WSU Research Foundation

Abstract

For many years silver has been used as a broad spectrum antimicrobial agent, applied towards reducing infections of burn victims, water treatment, treating textiles, among others. With an increasing amount of antibiotic-resistant bacteria, the utility of silver coatings and treatments are again being recognized as a cost- effective way to prevent bacterial infections such as for medical implants. This is especially crucial when surgeries are performed in environments where sanitation is not ensured.

This WSU invention relates to the use of silver coatings on medical implants as a valuable addition to promote antimicrobial properties such as resistance to growth of Gram negative bacteria (e.g., Pseudomonas aeruginosa). In an effort to optimize antimicrobial effectiveness and keep human cell-toxicity to a minimum, WSU inventors have experimented with various coating parameters and observed their effects on the utility of silver coating on SIGN stainless steel implants.

Applications and Advantages

Silver deposited implants offer to reduce growth of infection due to biofilm formation and aid fracture healing.

IP Status 

US patent application pending

Abstract

WSU inventors have developed epoxy resin systems and carboxylic terminated polyesters using rosin acids as building blocks. This provides a method to make epoxy resin systems that do not contain Bisphenol A (BPA).

Current powder coating polyester resins are built largely on tere-or isophthalic acid and trimellitic anhydride as rigid monomers together with other reactants. The epoxy resin is either diglycidyl ethers of bisphenol A or epoxy-novolac resin, both are based on the phenol building block.

Rosin and derivative as adhesive tackifier is a well established practice, and they have also found many other niche applications in inks, varnishes, paints, sealing wax, adhesives, some soaps, dressing for machine belting; paper sizing; soldering, plasters, etc.

With an annual global growth of 7%, powder coating is the fastest growing business in coating industry. The global powder coatings market was $3.3 billions in 2002. The projected production will be 1,460,000 tons in 2006 and will increase to 2,295,000 by 2010. Among other advantages, the solvent-free process, ease of application, and few wastes are most impressive. Powder coatings include epoxy, polyester­epoxy, polyester, polyurethane, acrylic and others. Polyester epoxy hybrid coating takes almost half of total market. Powder coating is widely applied in automotive, furniture, wood, construction, appliance industries.

Applications and Advantages

• Environment-friendly procedure and non-hazardous product output to humans
• Wide application due to enhanced properties: great peeling properties and impact strength

IP Status 

US patent and PCT applications pending

Publication  

Honghua Wang, Bo Liu, Xiaoqing Liu, Jinwen Zhang and Ming Xian. Synthesis of Biobased Epoxy and Curing Agents using Rosin and the Study of Cure Reactions. Green Chem., 2008, 10, 1190-1196

Abstract

Low density, low stiffness load-bearing implant structures are a dream for orthopedic surgeons. In total hip replacements (THR), dense metals with high density, high stiffness, and strength than natural bone is traditionally used as implant to replace the diseased or damaged hip, and help restore the natural hip function of the patient. Typical lifetime of a THR, however, is only seven to twelve years, and this lifetime has remained constant over the past 50 years. Low density and low stiffness implants are believed to increase the lifetime of THRs and researchers through time have attempted to produce natural bone-like properties implants but failed in most cases.  

Using metal-based rapid prototyping process, WSU inventors have developed a process to create functional load-bearing implants yet low density and low stiffness. Our inventors have reduced the overall stiffness and weight of the implants to 30-50% without changing its composition, size, and shape. The process they have developed can also be modified to add surface porosity for better biological fixation/bonding.

Applications and Advantages

■  Reduced stiffness and weight. Stiffness and weight reduced by 50% or more without changing the implant composition, size or shape.

■ Further aspects of this design optimize the implants' compositional similarities with natural bone:

- Improved biological fixation. The addition of calcium phosphates to create compositionally gradient porous structures enables tissue to grow through the pores and bond significantly better compared to any dense implants;

- Increased surface bioactivity. Nano-porous TiO2 surface modifications are applied via an intelligent modification approach which optimizes cell-materials interactions for early stage cell adhesion and proliferation.

IP Status

US patent application

Abstract

Wood-plastic composite is a very promising and sustainable green material that is produced for its ability to be durable without containing toxic chemicals. WSU has patented an invention that relates to the low-cost and efficient procedure of making low density cellular wood plastic composite with wood flour and high-density polyethylene wherein the ratio of wood flour to high-density polyethylene ranges from 1:4 to 3:2.  The following three steps outline this process of producing cellular wood plastic composite:

1)   mixing finely ground wood flour with plastic in an extruder to form a plasticated mixture;

2)   introducing a blowing agent into the plasticated material under pressure sufficient to drive the blowing agent into the plasticated mixture to form cells within the plasticated mixture, wherein the blowing agent is introduced under a pressure gradient in the extruder sufficient to increase the solubility of the blowing agent in the plasticated mixture and under a temperature sufficient to prevent collapse of the cells; and

3)    reducing the pressure prior to removing the plasticated mixture from the extruder.

Applications and Advantages

■  stable and low density;

■  use of low-cost materials for production (i.e. blowing agent);

■  better product output: increased stiffness

IP Status 

US Patent 7,431,872; Australia 2002259018; New Zealand 529062. Several others pending in Canada, Europe, Japan, and Mexico

Abstract

Bulk metallic glasses or bulk amorphous alloys (BAAs) have excellent glass forming ability and reduced glass transition temperatures leading to formation of amorphous structure at lower critical cooling rates of the order of 10³ K/s. In the recent years, multi-component Fe-based bulk amorphous alloys (BAAs) have attracted attention due their potential industrial applications in the areas where high wear and corrosion resistance are important. The excellent soft magnetic characteristics, high strength and good thermal stability of Fe-based amorphous alloy led to the development of new magnetic materials. However, downsides of this material, including limited amorphous phase-forming ability and high quenching rate, limited their structural processing in making bulk net shape BAA parts and wide industrial applications. 

WSU inventors were able to develop a process to demonstrate that net shape bulk amorphous components, for structural applications, can be fabricated using laser engineered net shaping (LENS ) by exploiting its current capabilities. LENS^TM  is an advanced rapid manufacturing technology offering the possibility of producing non-equilibrium microstructural features in metallic coatings and net shape components.

Applications and Advantages

■  LENS^TM  process can be used to investigate and fabricate structural parts using existing and new bulk amorphous alloys

■  SIGNIFICANT reduction of corrosion on treated metal surfaces.

Abstract

This technology utilizes novel probes to detect and identify target biomolecules in a sample. These probes employ conformational changes induced by molecular recognition events to initiate changes in the optical properties of the probe (e.g. the modulation of a fluorescence or absorption response upon target binding). Methods, including solid phase synthesis techniques for making probe molecules have been developed.

Applications and Advantages

■  Versatile approach to molecular recognition

■  Hairpin formation not a prerequisite for self association

■  Optical response can be tailored to application

■  Multiple targets can be probed simultaneously

■  Both the composition and nature of the probes and reporters can be modulated

IP Status 

US Patent Nos. 7,238,792; 7,556,967

Publications

Han, Jason J.; Wang, Wei; Li, Alexander D. Q.. Folding and Unfolding of Chromophoric Foldamers Show Unusual Colorful Single Molecule Spectral Dynamics. Journal of the American Chemical Society (2006), 128(3), 672-673.

Wang, Wei; Wan, Wei; Stachiw, Andrew; Li, Alexander D. Q.. Foldamers with Hybrid Biological and Synthetic Sequences as Selective DNA Fluorescent Probes. Biochemistry (2005), 44(32), 10751-10756.

Wang, Wei; Wan, Wei; Zhou, Hong-Hui; Niu, Shuqiang; Li, Alexander D. Q.Alternating DNA and ï° -conjugated sequences. Thermophilic foldable polymers. Journal of the American Chemical Society (2003), 125(18),5248-5249.

Wang, Wei; Li, Lin-Song; Helms, Greg; Zhou, Hong-Hui; Li, Alexander D. Q.. To Fold or to Assemble? Journal of the American Chemical Society (2003), 125(5), 1120-1121.

Abstract

The invention relates to implant for total hip replacements or fixing physical hip joints damage. Using metal-based rapid prototyping process, WSU inventors have developed a process to create functional load-bearing implants yet low density and low stiffness.

Low density, low stiffness load-bearing implant structures are a dream for orthopedic surgeons.  In total hip replacements (THR), dense metals with high density, high stiffness, and strength than natural bone is traditionally used as implant to replace the disease or damaged hip and help restore the natural hip function of the patient. Typical lifetime of a THR, however, is only seven to twelve years, and this lifetime has remained constant over the past fifty years. Low density and low stiffness implants are believed to increase the lifetime of THRs and researchers through time have attempted to produce natural bone-like properties implants but failed in most cases. Our inventors have reduced the overall stiffness and weight of the implants to 30-50% without changing its composition, size, shape. The process they have developed can also be modified to add surface porosity for better biological fixation/bonding.

Applications and Advantages

■  Reduced stiffness and weight. Stiffness and weight reduced by 50% or more without changing the implant composition, size or shape.

■  Further aspects of this design optimize the implants' compositional similarities with natural bone:

1.    Improved biological fixation. The addition of calcium phosphates to create compositionally gradient porous structures enables tissue to grow through the pores and bond significantly better compared to any dense implants.

2.    Increased surface bioactivity. Nano-porous TiO2 surface modifications are applied via an intelligent modification approach which optimizes cell-materials interactions for early stage cell adhesion and proliferation.

IP Status 

US and Indian patent applications pending.

Publications

US Patent Publication No. 2007-0203584 A1

Abstract

Advanced resorbable biomaterials are important toward improving health care, by enabling quicker restoration of functionally loaded natural bone. Synthetic calcium phosphates have properties similar to natural bone, but they lack the mineral content inherent to bone. WSU researchers have developed calcium phosphate-based resorbable ceramics with select dopants, optimized for in vitro degradation and cell-materials interactions as a function of time.

Applications and Advantages

Improved cell materials interactions: Early stage cell adhesion and proliferation is significantly enhanced.

Controlled strength degradation: The addition of particular dopants to resorbable calcium phosphates enables the material to degrade at a controlled rate which closely matches the re-growth rate of the natural bone.  The invention has broad application possibilities:

■  bone grafts and fusions

■  surgical plates and screws

■  dental implants

■  coatings

IP Status  

US patent and PCT applications pending

Abstract

Currently in development at WSU is a methodology to make super-toughened polylactic acid (PLA) blends in which PLA content is more than 80 wt%. The resulting blends display not only super toughness (impact strength >800 J/m) but also high ductility (tensile elongation > 200%) and moderate tensile strength.

Applications and Advantages

■   Bio-degradable

■   Good impact toughness

■   Meltprocessability

IP Status 

US patent application(s) pending

Abstract

This invention deals with surface modification of implants.  More specifically, it focuses on the simultaneous improvement of bone cell materials interactions and anti-microbial activity.  The results focus on surface treatment methods to simultaneously enhance tissue integration while reducing chances of infection that can be applied as a post-processing operation to metallic implants such as hip, knee, and spinal devices as well as screws, pins, and plates.

Applications and Advantages

■   Offers to enhance cellular adhesion and promote growth of natural bone cells while preventing microbial activities

■   Reduces need for antimicrobial medications post surgery

IP Status 

US patent application pending, FDA approval pending (trials underway)

Abstract

The commercial need for Lithium-ion batteries is increasing exponentially year over year as more mobile devices and automobiles take advantage of advanced energy storage for better performance. A unique drawback of these batteries, however, is that their energy density and life span are severely reduced from the theoretical potential due to manufacturing limitations of the currently used cathode and anode materials.

Currently, WSU scientists have developed a method that offers a significant breakthrough in Li-ion battery technology. This invention focuses on synthesizing Tin nanoneedles by electrochemical processes without  templates for use as anode material. These nanoneedles have never been synthesized either by vapor transport, or other electrochemical methods.  The use of these Tin nanoneedles in Lithion-ion batteries results in a five to ten times increase in battery capacity and significantly increases the lifespan of the battery. Testing has showed that batteries with over 200 full discharges show no significant reduction in capacity.

Applications and Advantages

This PCT patent-pending WSU technology is a simple, cost-effective and commercially scalable electrochemical method for the synthesis and production of Tin ‘nanoneedles’ that can be used as an anode material in Li-ion batteries. The Tin ‘nanoneedles’ also have commercial applications in the construction of semi-conductors, capacitors and sensor materials.

IP Status

US and PCT applications for the methods of production and specific application of use in Lithium Ion batteries.

Abstract

A processor for an FM/CW sensor divides the sweep periods of the sensor into a number of subsweep intervals, measures the received power within a multiplicity of frequency windows during each of the sub-sweep intervals, and then performs a spectrum analysis of the power measurements in each frequency window to characterize the reflectors in the corresponding range bins of the FM/CW sensor footprint.

Applications and Advantages

■   Offers a small, low cost target seeking radar that is: accurate over conventional missiles; offers a great deal of resolution; employs conventional linearized transmitters; and recognizes targets very quickly to minimize sensitivity to circuit drifts and missile velocity .

IP Status 

US Patent 5,339,082

Abstract

The position of an aircraft control surface actuator is determined by a combination of a linear transducer and light radar.  A link has a first end attached to a magnet and a second end attached to the actuator.  Movement of the actuator causes the magnet to move axially along the outer cylindrical surface of a hermetically sealed housing.  The transducer includes a magnetic coupling between the magnet end and a ferromagnetic follower inside the sealed housing. Preferably, the magnet is a ring magnet, and the ferromagnetic follower is a tubular cylinder.  The follower carries a corner cube reflector that receives light from, and reflects light back to, the end of an optical fiber.  The transit time of the light is measured and is used to calculate the distance between the fiber end and the reflector to thereby determine the position of the actuator.  The hollow configuration of the follower increases magnetic flux exiting from the flat end surfaces of the follower to increase the strength of the magnetic coupling and also reduces the mass of the follower to reduce displacement inaccuracy during acceleration.  The length of the follower is preferably equal to the distance between the poles of the magnet.

Applications and Advantages

■   Provides a highly reliable, accurate, and cost-effective system;

■   Provides accurate and reliable determination of the position of aircraft structures, such as control surface actuators;

■   Simple structures that allows minimization of sensing system and easy inclusion in new aircraft designs;

■   Unaffected by environmental conditions such as temperature and pressure.

IP Status 

US Patent No. 5,247,172

Abstract

This technology relates to a new PCR diagnostic test developed here at WSU for the detection of caulimoviruses. This test is useful for broad spectrum detection of caulimos. Some of the tested members include CaMV, Figwort mosaic virus, Dahlia mosaic virus, carnation etched ring virus, Horseradish latent virus and Mirabilis mosaic virus.

Members of the genus Caulimovirus are characterized by a double-stranded DNA genome of about 8 kb in size and they infect a wide range of crops. Considerable divergence exists in the genomic sequences of these viruses.  As a result, virus-specific probes have to be used for their diagnosis. Tools that could detect a wide range of caulimoviruses in a single test would be rapid and less expensive.  Based on conserved regions of known caulimovirus genomes, degenerate primers were designed and used in a polymerase chain reaction-based assay.  Several members of the genus could be detected using these primers.  The method facilitates rapid diagnosis of caulimoviruses in crops.

Applications and Advantages

Facilitates rapid and economical diagnosis of caulimoviruses in crops

Publication

Pappu, H.R., and K.L Druffel. 2008. A group-PCR assay for the detection of members of the genus Caulimovirus. Annual meeting of the American Phytopathological Society, July 26-30, 2008. Minneapolis, MN. Phytopathology 98 (supplement). http://www.apsnet.org/

Abstract

The technology is related to genes encoding plant acyl-CoA thioesterases from Arabidopsis and methods of their use.  Fatty acids have been extensively exploited for industrial uses in products such as lubricants, plasticizers, and surfactants. In fact, approximately one-third of vegetable oils produced in the world are already used for non-food purposes. Manipulating the genes in the triacylglycerol (TAG) synthesis pathway can contribute to altered or increased fatty acid content in oilseeds.

Most of the efforts to modify TAG content have focused on either increasing the nutritional characteristics and chemical stability of edible oils or on introducing new and unusual fatty acids into TAGs for use in various industrial applications. Progress has been achieved through over-expression and/or suppression of a modestly small number of genes in the TAG synthesis pathway. However, to date, the alterations in fatty acid content have not been substantial enough to create truly meaningful new oilseed lines. Thus, this technology has the potential to increase the TAG content in transgenic crops.

Applications and Advantages

■  Has the potential to develop plants containing specialized fatty acid compositions;

■  Offers to increase the triacylglycerol content in transgenic crops.

IP Status

Patents issued: US (6,878,861); and several others pending. 

Abstract

This invention relates to a peptide signal for inducing plant defense response against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium. There is todate, no direct evidence for the involvement of endogenous peptide signaling in the activation of either local or systemic microbial pathogen defense responses in plants.

WSU inventors have isolated a peptide from Arabidopsis thaliana that acts as a signal for defense against pathogen attacks.

The signal induces the transcription of several known defense genes of Arabidopsis including a defensin gene, a tyrosine amino transferase gene and two PR protein genes, as if the plants were being infected by pathogens. These genes are well characterized genes that are inducible in Arabidopsis leaves in response to pathogen attacks. The gene orthologs have been identified in several other crop plants including rape, soybeans, alfalfa, potato, poplar and rice. These agriculturally important plants are of widely diverse evolutionary origins, indicating that the peptide may be a universal signal in plants for defense against pathogens.

Applications and Advantages

■   Offers a distinct advantage to the plants in mounting resistance responses against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium;

■   Provides a way of constitutively over-expressing natural defense genes, prior to pathogen attacks.

IP Status

US patent application pending

Publication 

Huffaker, Alisa; Ryan, Clarence. 2008. PROPEP Family Regulation of Pathogen Defense in Arabidopsis thaliana. Plant Biology 2008. Organized by the American Society of Plant Biologists. June 26 - Tuesday July 1, Mérida, Mexico

Abstract

An 8 amino acid peptide was isolated from soybean leaves that is capable of alkalinizing the media of soybean suspension cells, a response that is generally associated with defense peptides.  The peptide was found to be active at low concentrations with an extremely fast response time.  The peptide is located on the carboxy-terminal end of a precursor protein deduced from a est library and found to induce defense genes.  This and a homologue were both highly expressed in the roots, relative to the aerial portions of the plant.  Treatment of the aerial portion of soybean plants with hormones involved in elicitation of defense responses revealed a significant increase in expression levels.

Abstract

This invention relates to a peptide signal for inducing plant defense response against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium. There is to date, no direct evidence for the involvement of endogenous peptide signaling in the activation of either local or systemic microbial pathogen defense responses in plants.

WSU inventors have isolated a peptide from Arabidopsis thaliana that acts as a signal for defense against pathogen attacks. The signal induces transcription of several known defense genes of Arabidopsis including a defensin gene, a tyrosine amino transferase gene and two PR protein genes, as if the plants were being infected by pathogens. These genes are well characterized genes that are inducible in Arabidopsis leaves in response to pathogen attacks. The gene orthologs have been identified in several other crop plants including rape, soybeans, alfalfa, potato, poplar and rice. These agriculturally important plants are of widely diverse evolutionary origins, indicating that the peptide may be a universal signal in plants for defense against pathogens.

Applications and Advantages

■  Provides a way of constitutively over-expressing natural defense genes, prior to pathogen attacks;  

■  Provides a distinct advantage to the plants in mounting resistance responses against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium. 

Publication

Pearce, G., Y. Yamaguchi , G Munske and C.A. Ryan. 2008. Structure-activity studies of AtPep1, a plant peptide signal involved in the innate immune response. Peptides 29: 2083-2089.

Abstract

How carbon flux differentially occurs in vascular plants for protein synthesis, phenylpropanoid metabolism (i.e. lignins) and other metabolic processes is not well understood. Having previously discovered/validated that a six-membered arogenate dehydratase (ADT 1-6) family encodes the final step in Phe biosynthesis in Arabidopsis thaliana, this raised the fascinating question whether individual ADT isoforms (or combinations thereof) differentially modulated carbon flux to lignins, proteins, etc. WSU scientists obtained homozygous T-DNA insertion lines for 5 of the 6 ADTs, these being used to generate double/triple knockouts in all possible combinations. Various mutants gave phenotypes with profound but distinct reductions in lignin amounts and not accompanied by gross anatomical/growth and development defects, such as dwarfing. This is the first example of a plastid-localized metabolic step profoundly affecting carbon flux into lignin.

Applications and Advantages

This invention can facilitate further research, and development to further unravel the complexities of lignin biosynthesis at the cellular and tissue levels. Moreover, this offers opportunity to establish: specific roles of each ADT in various aspects of phenylpropanoid and lignin forming metabolic processes, including detailed metabolomic analyses, and a new means to probe lignin primary structure as well as the physiological consequences of lignin deposition reduction. Potential applications include controlling lignin flux where increased lignin can be exploited for production of commercially valuable compounds while decreased lignin can be exploited in the field of bioenergy.

IP Status

US provisional patent application pending

Publication

Man-Ho Cho, Oliver R. A. Corea, Hong Yang, Diana L. Bedgar, Dhrubojyoti D. Laskar, Aldwin M. Anterola, Frances Anne Moog-Anterola, Rebecca L. Hood, Susanne E. Kohalmi, Mark A. Bernards, ChulHee Kang, Laurence B. Davin, and Norman G. Lewis. Phenylalanine Biosynthesis in Arabidopsis thaliana. Identification and Characterization of Arogenate Dehydratases. The Journal of Biological Chemistry. 2007, 282 (42), 30827-30835

Abstract

Brassinosteroids are plant-specific steroid hormones and are known to play an important role in coupling environmental factors, especially light, with plant growth and development.  Ca²⁺/calmodulin plays an essential role in sensing and transducing environmental stimuli. Arabidopsis DWARF1 (DWF1) is responsible for an early step in brassinosteroid biosynthesis that converts 24-methylenecholesterol to campesterol. 

WSU inventors discovered that DWF1 is a Ca²⁺/calmodulin-binding protein and this binding is critical for its function.  Our inventors showed that loss of calmodulin-binding totally abolished the function of DWF1 in planta, while partial loss of calmodulin-binding resulted in a partial dwarf phenotype in complementation studies.  These results provide direct proof that Ca²⁺/calmodulin-mediated signaling plays a critical role in controlling the function of DWF1 which could be used to producing size-engineered crops by altering the Ca²⁺/calmodulin-binding property of their DWF1 orthologs. DWF1 orthologs from other plants have a similar Ca²⁺/calmodulin-binding domain, implying that Ca²⁺/calmodulin regulation of DWF1 and its homologs is common in plants.

Applications and Advantages

The discovery by WSU scientists provides a new biotechnological approach to produce semi-dwarf or size-engineered plants. This approach is applicable to a wide range of plants, and is valuable for crop breeders.

IP Status

US patent application pending.                    

Publication

Du, L. and Poovaiah, BW. 2005. Ca²⁺/calmodulin is critical for brassinosteroid biosynthesis and plant growth. Nature 437(7059):741-745.

US Patent Publication No. US20070089183A1

Abstract

Intracellular calcium transients during plant-pathogen interactions are necessary early events leading to local and systemic acquired resistance. Salicylic acid, a critical messenger, is also required for both these responses,  but whether and how salicylic acid level is regulated by Ca2+ signaling during plant-pathogen interaction is unclear.  Here a novel mechanism connecting Ca2+ signal to salicylic acid-mediated immune response through calmodulin, AtSR1/CAMTA3, a Ca2+/calmodulin-binding transcription factor, and EDS1, an established regulator of salicylic acid level, is reported.  Constitutive disease resistance and elevated levels of salicylic acid in loss-of-function alleles of AtSR1/CAMTA3 suggest that AtSR1 is a negative regulator of plant immunity.  This was confirmed by epistasis analysis with mutants of compromised salicylic acid accumulation and disease resistance.  This WSU research shows that AtSR1 interacts with the promoter of EDS1 and represses its expression.  Furthermore, Ca2+/calmodulin-binding to AtSR1 is required for suppression of plant defense, indicating a direct role for Ca2+/calmodulin in regulating the function of AtSR1.  These results revealed a novel regulatory mechanism linking Ca2+ signaling to salicylic acid level.

IP Status

US patent application filed

Publication(s)

US patent pub No. US-2010-0223690-A1

Abstract

WSU scientists have recently unveiled the previously unknown regulatory mechanism linking calcium signaling to salicylic-acid-mediated responses, both implicated for regulating plant disease-resistance response. Working on a model plant Arabidopsis thaliana, they showed that AtSR1 (Arabidopsis thaliana signal responsive 1), a calcium/calmodulin-binding transcription factor, is a negative regulator of plant immunity since it suppresses the biosynthesis of salicylic acid, a hormone that promotes disease resistance. Plants with loss-of-function alleles of AtSR1 have elevated expression of genes associated with systemic acquired resistance and displayed enhanced resistance to pathogens such as Pseudomonas syringae. They discovered that these changes coincide with increased production of salicylic acid and that the repression of the immune response by AtSR1 is regulated by calcium/calmodulin.

The constitutive loss of AtSR1 has enhanced plant disease reistance yet resulted in reduced plant growth, which is not advantageous for commercial applications. To overcome this, the same group of WSU scientists has conditionally reduced the function of AtSR1 using an inducible promoter-driven antisense or RNAi (RNA interference) construct of AtsR1. Crops transformed using the RNAi construct resulted in a stable modification of the biochemical pathway, resulting in disease-resistant phenotypes without affecting plant growth.

Applications and Advantages

The invention offers to revolutionize breeding programs focused on disease resistance without sacrificing growth and yield for almost every agronomic crop. It can also facilitate research, development, and expansion of the use of RNAi technology for determining other function of genes related to disease resistance and other stress-related traits.

IP Status

Available for licensing

Abstract

This invention offers a method to diagnose Iris Yellow Spot Virus (IYSV) in onions. Iris yellow spot virus (IYSV) is an economically important viral pathogen of onion.  The virus was first confirmed in Washington State in 2004.  Since then, the virus spread rapidly to all the onion growing counties, including Walla Walla, causing significant losses in both bulb and seed crops. Growers have limited control options.  Existing commercially available antisera are not sensitive enough, resulting in false negatives. 

Antiserum specific to the nucleoprotein gene of IYSV was produced and tested for its specificity to detect the virus. The antiserum reacted specifically with its homologous antigen, IYSV when tested in an indirect-ELISA format. The antiserum was found to be specific to IYSV and did not react with the other two tospoviruses present in the US (Impatiens necrotic ring spot virus and Tomato spotted wilt virus). The antiserum was further characterized for its titer and sensitivity of detection. IYSV could be detected in up to 1:100 dilutions of the plant extract and the antiserum was able to detect the virus at 1:6400 dilution.                                                    

Applications and Advantages

Offers a rapid and sensitive assay for diagnosis of Iris Yellow Spot Virus in onions.         

Abstract

Improvements in plant productivity (biomass) and yield have centered on increasing the efficiency of leaf carbon dioxide fixation and utilization by non-photosynthetic sink organs. This technology focuses on exploiting leaf starch synthesis as a transient sink to increase plant productivity and yields. In particular, transgenic Arabidopsis were used as examples where mutant transgenic plants were shown to exhibit enhanced photosynthetic capacity that translated into increased growth and biomass.  

Applications and Advantages

• Offers a viable alternative strategy to increase productivity and yields of crop and bio-energy plants.

IP Status

US provisional patent

Abstract

This technology involves the production of chavicol/eugenol and potential and current applications in antibacterials/plant defense/analgesics, polymer building blocks, and in biofuel/bioenergy production.

One of the major potential sources of renewable energy/biofuels being considered is that from plant biomass, i.e. through fermentation of polymeric carbohydrates to give ethanol.  There are two major scientific hurdles that have not yet been overcome in this process.  The first is that of the polymeric lignins, which make up ca. 20-30% of all plant stem biomass, and which are nature’s second most abundant organic materials. Under current fermentation processes, lignins cannot readily be converted into either ethanol and/or other liquid/gaseous fuels.  Indeed, there are still no isolated enzymes and/or proteins known to effectively degrade the lignin macromolecules. Secondly, the polymeric lignins themselves represent a formidable physical barrier in biomass for efficient carbohydrate fermentation. Thus, their presence represents a critical barrier in making these technologies more economical.  WSU’s proposed solution to these is diverting monolignol flow away from lignin biopolymer formation, or from heartwood lignan accumulation/deposition, to that engendering formation of the potential product liquid fuels/intermediate chemicals of interest i.e., eugenol and chavicol. This WSU technology, hence, focuses in the:

■ production of chavicol/eugenol in bacterial and plant cell cultures;

■ transformation of either oilseed (e.g., rapeseed) or heartwood-forming plants to produce, in large quantity, chavicol and eugenol;

■  production of the biopolymers or intermediates for the chemical industry; and

■  making cellulosic ethanol production more efficient by virtue of less lignin and easier fermentation                       

Applications and Advantages

■        offers methods for redirecting carbon allocation in plants or cell culture from lignification to more useful and tractable materials, and to facilitate the generation of, e.g. biofuels from the remaining plant to culture biomass; and

■     provides a novel way to more effectively utilize the lignin biopolymers and/or the carbon allocated for the lignin-forming pathway.

IP Status

US, and Europe patent applications pending

Publication

US patent publication no. US20100031398 A1

Europe patent publication no. EP 2046110

Vassão, DG, Kim SJ, Milhollan JK, Eichinger D, Davin LB and Lewis NG. (2007).  A pinoresinol-lariciresinol reductase homologue from the Creosote bush (Larrea tridentata) catalyzes the efficient in vitro conversion of p-coumaryl/coniferyl alcohol esters into the allylphenols chavicol/eugenol, but not the propenylphenols p-anol/isoeugenol. Archives of Biochemistry and Biophysics 465. 209–218

Abstract

The invention is a new wheat genotype, with tolerance to glyphosate herbicide at practical application levels. This genotype was developed via traditional mutation breeding and selection and did not involve transgenic approaches.

Weed control is the primary yield limiting factor in wheat production, which impacts essentially every acre in commercial production worldwide.  Cost effective, efficient, environmentally friendly weed control methods are essential to sustainable wheat production.  This discovery offers the possibility of creating non-transgenic, glyphosate tolerant wheat cultivars.  Gene(s) associated with glyphosate tolerance identified through this research could be introgressed into adapted germplasm from every wheat producing region in the world through conventional breeding, eliminating market acceptance and perception issues against transgenic crops.

Applications and Advantages

■  Non-transgenic technology that offers growers/farmers reduce mechanical weed control by selectively and effectively controlling glyphosate sensitive weeds after crop emergence;

■  Offers improved weed control that may eventually lead to no-till wheat production, resulting to enhanced profitability and likewise promoting for economic and environmental sustainability in wheat farms. 

IP Status

US and PCT applications pending    

Publication

PCT publication WO 2007092505 A2

Abstract

Among the arsenal of plant-derived compounds activated upon attack by herbivores and pathogens are small peptides that initiate and amplify defense responses. However, only a handful of plant signaling peptides have been reported.  WSU inventors have isolated a 12 amino acid peptide from soybean (Glycine max) leaves which causes a pH increase of soybean suspension-cultured cell media within 10 min at low nanomolar concentrations, a response that is typical of other endogenous peptide elicitors and pathogen-derived elicitors. The amino acid sequence was determined and a synthetic peptide, when supplied to soybean cultures, induced the expression of known defense-related genes.

Applications and Advantages

This invention presents exciting new possibilities for understanding basic mechanisms of plant protection. The uniqueness of the nucleotide sequence may provide a site for genetic manipulation for expressing other defense peptides.

IP Status

US patent application pending

Abstract

Grapevine leafroll disease (GLRD) is an economically important virus disease to the sustainability of the grape and wine industry in Washington State.  An infectious cDNA clone (GLRaV-3) that has been developed by WSU researchers will help apply reverse genetics to study the molecular biology of grapevine-infecting closteroviruses and the etiology of GLRD.  The cDNA clone has the potential to be used as a vector to express foreign genes and heterologous proteins in grapevine and is amenable for use as a vector for studies on virus-induced gene silensing (VIGS) in grapevine.

The cDNA clone is the most prevalent worldwide among all GLRaVs and can be spread by insect vectors like mealybugs and scale insects.  The clone is taxonomically aligned more closely with other GLRaVs (genus Ampelovirus, family Closteroviridae) and is the type member of the genus Ampelovirus, which includes viruses causing serious diseases in other agriculturally important perennial crops like pineapple (Pineapple Mealybug Wilt-associated Virus 1), cherries (Little Cherry Virus 2) and plums (Plum Bark Necrosis Stem Pitting-associated Virus). The clone's vector system would provide basic knowledge that has potential practical value to similar viruses infecting other perennial fruit crops.

IP Status

Available for licensing  

Abstract

Final fruit diameter is the prime determinant of sweet cherry value.  Poor fruit set limits yield and profitability in sweet cherry.  Certain plant growth regulators have been shown to be effective in enhancing fruit growth, when applied at the right stage of fruit development.  In ‘Bing’ cherry, for example, WSU researchers have discovered that a particular plant growth regulator improved fruit set by 70-100%, with final fruit size 10-20% higher than in untreated trees.  Experiments with two other cherry species showed similar results.  Based on this mode of action in sweet cherry, this WSU invention has potential applications in other stone fruit cultivars.

IP Status

US patent application

Abstract

This technology is a new method of transforming cereals for transferring desirable genes.  This method involves dipping spikes of cereals into Agrobacterium harboring the plasmid and gene of interest.  The production of transgenic seed can be achieved in 3 months. The use of Agrobacterium allows for single or low copy gene insertion.  This involved determining the best Agrobacterium strain, the genotype most amenable to transformation, changing the infiltration media, and determining the optimal age of transformation.

Applications and Advantages

■  Offers a new, faster and cheaper method of transforming cereals to enable transfer of desirable genes;

■  Offers to address issues of multiple genes insertions and subsequent gene silencing, all problems associated when using biolistics.

IP Status

US patent application pending 

Publication

Zale, J., Agarwal, S., Loar, S., Steber, C.M. 2009. Evidence for stable transformation of wheat by floraldip in Agrobacterium tumefaciens. Plant Cell Reports 28(6):903-913.                  

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/ lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants: enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,635,459; 6,210,942), Australia (728116) and several others pending. 

Abstract

This technology relates to the utility of using RT-PCR technique to detect whether or not climacteric fruit have been subjected to treatment with a commercial inhibitor of ripening. 1-MCP, the inhibitor, is effective as a gas treatment at levels of 1ppm or lower and does not leave detectable residue on the produce while fostering somewhat dramatic effects on the progression of ripening, hence deterioration of fruits that require ethylene gas, a naturally-occurring plant hormone, to initiate the onset of ripening.  Fruits that require ethylene synthesis and perception to ripen are termed climacteric fruits.  Upon ethylene perception, a cascade of biochemical changes associated with the ripening process proceeds, resulting in a ripened commodity with optimal fresh eating quality.  By use of specific primers for ripening-associated gene expression, 1-MCP treatment is easily detectable using RNA extracted from the fruit.

Applications and Advantages

Use of reverse-transcriptase polymerase chain reaction (RT-PCR) offers rapid detection and quantification whether or not climacteric fruit have been subjected to treatment with ripening inhibitors such as 1-methylcyclopropene (MCP), an ethylene perception inhibitor.

Abstract

Chilly temperatures can ruin an entire sweet cherry crop. Winter cold or spring frost injury may weaken plant parts and give systemic, symptomless bacterial colonies the conditions conducive to rapid growth, leading to disease symptoms.Frost, especially when closely followed by rain or heavy dew, leads to bacterial blast of blossoms, hence affects fertilization and fruit set. WSU researchers have developed a novel product, including its timing of applications, for frost protection in sweet cherry. Optimal spraying of this product to sweet cherry significantly improved bud formation and flower hardiness, translating to improvement of fruit, set, leaf growth, and fruit size. Based on this mode of action in sweet cherry, this WSU invention has potential applications in other fruit crops.

Applications and Advantages

■  Offers a novel and effective technique of reducing crop losses in sweet cherry due to frost

IP Status

US patent application pending 

Abstract

The technology is related to genes encoding plant acyl-CoA synthetases (ACS) from Arabidopsis and methods of their use. Fatty acids have been extensively exploited for industrial uses in products such as lubricants, plasticizers, and surfactants. In fact, approximately one-third of vegetable oils produced in the world are already used for non-food purposes. Manipulating the genes in the triacylglycerol (TAG) synthesis pathway can contribute to altered or increased fatty acid content in oilseeds.

Most of the efforts to modify TAG content have focused on either increasing the nutritional characteristics and chemical stability of edible oils or on introducing new and unusual fatty acids into TAGs for use in various industrial applications. Progress has been achieved through over-expression and/or suppression of a modestly small number of genes in the TAG synthesis pathway. However, to date, the alterations in fatty acid content have not been substantial enough to create truly meaningful new oilseed lines. Thus, this technology has the potential to increase the TAG content in transgenic crops.    

Applications and Advantages

■  Has the potential to develop plants containing specialized fatty acid compositions;

■  Has the potential to increase the triacylglycerol content in transgenic crops.      

IP Status

Patents issued in: US (7,105,722); and several others pending. 

Abstract

After nearly a decade of research, WSU scientists have discovered new ways to trigger quicker response and elucidate defense mechanisms of plants against stem rust, and potentially to defeat the deadly wheat steam rust race TTKSK (also known as Ug99). Stem rust, caused by the fungus Puccinia graminis (P. graminis), is a virulent disease that can destroy a grower's entire crop and affects wheat, barley, rye, and others. The recent appearance of its new strain Ug99 poses further threats to the cereal industry worldwide.

Our researchers worked on the barley stem rust R gene, Rpg1 (Reaction to P. graminis 1), which provides durable resistance to the stem rust pathogen P. graminis f. sp. tritici, a trait highly desirable and very relevant to barley and wheat breeding. Their recent in vivo findings revealed that the combined action of two avirulent spore effectors applied on the leaf surface of the barley plant works to activate plant defenses (as quick as 5 min) prior to pathogens arrival. This results to enhanced ability of the plant to fight off stem rust infection before it even starts. Concerted action of both identified proteins from stem rust pathogens triggered rapid phosphorylation and eventual degradation of Rpg1. The process initiates resistance to stem rust on the susceptible cultivar. These are breakthroughs that can revolutionize the fight against rust affecting cereal grains.

Applications and Advantages

The effects of Rpg1 and the discovery of the proteins that activate Rpg1-mediated resistance stem rust, together with the simple means of application (e.g. spray application) provide a strong basis for investment and commercialization of this WSU technology.

IP Status

Under review

Abstract

WSU researchers have developed a novel product that can, in combination with a common chemical, significantly improve fruit size, fruit quality, and postharvest characteristics in 'Bing' cherry. Use of the above product and the chemical improved fruit storability by maintaining fruit firmness, sweetness, and consumer appeal. The product alone, or in combination with the chemical, inhibited shoot growth and delayed fruit coloring. Overall, pre-harvest foliar application of the novel product and the chemical shows potential for affecting canopy source-sink relations and improved quality and shelf-life of 'Bing' sweet cherries.

IP Status

US patent application pending 

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.         

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants:    enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,210,942; 6,635,459) and several others pending.           

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants:  enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,911,330); New Zealand (508270) and several others pending. 

Abstract

This technology relates to the production of ricinoleic acid using transgenic technology. Ricinoleic acid is a hydroxylated fatty acid with great value as a petrochemical replacement in a variety of industrial processes. Its derivatives are found in products such as dyes, lubricants, nylon, soaps, inks, adhesives, and biodiesel. Current production of ricinoleic acid is worth over $100 million per year. The main commercial source of ricinoleic acid is the seeds of castor bean. However, castor is poorly suited to large-scale agricultural production. Also, the seeds of castor contain ricin, a highly poisonous protein, and produces allergenic proteins causing medicinal problems for workers cultivating and harvesting these plants. It is, therefore, desirable to develop a method that is better suited for large-scale agricultural production of ricinoleate-rich oils using other commodity crops (e.g. soybean or canola) that is less health-risk.

Two important genes have been identified in the pathway of ricinoleic acid metabolism found to provide enhanced production of ricinoleic acid in plants. One of these two genes increased the production of ricinoleic acid by up to 80%, to a total of 30% hydroxy fatty acids in the seed oil of transgenic Arabidopsis. Combining both genes to maximize the production of ricinoleic acid in crop plants are expected to increase production.

Applications and Advantages

■  Has a significant potential advantage over the traditional methods of processing castor bean as well as increasing the much needed supply of ricinoleic acid.

■  Offers to eliminate processing barriers associated with castor bean hence results to better quality ricinoleic acid

IP Status

US, Europe, and PCT applications pending 

Publication

Lu, C., Fulda, M., Wallis, J.G. and Browse, J. 2005 A High-Throughput Screen for Genes from Castor that Boost Hydroxy Fatty Acid Accumulation in Seed Oils of Transgenic Arabidopsis. Plant J. 45:847-856.

Abstract

The present invention relates to nucleic acid sequences which encode polypeptides having PhzO activity, namely, the ability to convert phenazine-1-carboxylic acid to 2-hydroxylated phenazines and isolated polypeptides having this activity.  The invention also relates to recombinant nucleic acid molecules, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing and using polypeptides, including expression in bacterial or plant cells to inhibit fungal pathogens.

Applications and Advantages

The use of the nucleic acid sequences are instrumental for the isolation of homologous genes from microorganisms to obtain genes which protect host cells, including bacteria, and plants against fungal pathogens.

IP Status 

US Patent 6,737,260; 7,189,547

Abstract

This technology relates to new diagnostic tests for the detection of Barley Yellow Dwarf Virus (BYDV). BYDV is an important pathogen of wheat, barley, corn, and oats.  The virus exists as several serotypes such as RPV, RMV, PAV, and SGV.  There are no rapid and sensitive methods for simultaneous detection of these serotypes.  WSU inventors have identified conserved regions within the RNA genomes of these serotypes and designed primers and developed an RT-PCR assay that can detect several serotypes in a single RT-PCR reaction.  A group test for these serotypes is now possible using standard RT-PCR or real-time PCR. Recombinant coat protein from BYDV was used to produce antisera for utilization in an ELISA-based assay and/or an immune-oblot assay for broad spectrum and specific detection of BYDV serotypes.

Applications and Advantages

■    Useful for broad spectrum detection of the c=virus in several crops.

Abstract

Camelina is one of the crops that is being actively explored and researched in recent days for its potential use as a biofuel crop. Value-added traits that would reduce input costs should aid in exploiting this crop as an alternative fuel crop. This particular technology relates to the use of Arabidopsis/Camelina derived AHL genes and gene products for modulation of cell growth in plants. Our WSU investigators have discovered that mutations within the A-T hook domain confer a dominant negative phenotype to the plants resulting in longer hypocotyls and taller seedlings. 

The practical utility of this discovery is that Camelina can be planted deeper enabling the growing seed to tap into deeper water sources.  This should make it particularly attractive and useful in dryland agriculture. In addition to its utility in Camelina, the mutants can be exploited in other crops of commercial value.

Applications and Advantages

Offers to transform the oilseed, camelina as a better biofuel crop using transgenic technology

IP Status 

US patent application pending

Publication 

Street IH, Shah PK, Smith AM, Avery N, and Neff MM (2008). The AT-hook containing proteins SOB3/AHL29 and ESC/AHL27 are negative modulators of hypocotyl growth in Arabidopsis. Plant Journal 54. 1-14.

Abstract

WSU inventors have discovered transformed (transgenic) biocontrol agents for control of plant root diseases. In particular, the invention is directed to biologically pure cultures of transformed strains of fluorescent Pseudomonas species (spp.) which have a biosynthetic locus which encodes for the production of the antibiotic phenazine-1-carboxylic acid stably introduced into the genome, and which suppress (inhibit the incidence of or reduce the incidence or severity of) diseases caused by the soil-borne pathogen Rhizoctonia. Optionally, the strains suppress diseases caused by Pythium or diseases caused by Gaeumannomyces graminis (Gg) in addition to diseases caused by Rhizoctonia, or have the ability to control all three diseases.

Root diseases caused by Rhizoctonia, Pythium, and Gaeumannomyces graminis, cause a significant adverse impact on the production of important crops worldwide. The root disease take-all, caused by Gaeumannomyces graminis var. tritici (Ggt), Rhizoctonia root rot, caused by Rhizoctonia solani and R. oryzae, and Pythium root rot caused by any of several Pythium species, notably, Pythium ultimum and P. irregulare, are important root diseases of small grain crops, e.g., wheat, barley, triticale, and rye, worldwide.

Applications and Advantages

■   Offers a sustainable and environment-friendly alternative approach to control take-all and other soil-borne diseases.

IP Status 

US Patent (6,277,625; 6,447,770); Lithuania (4785); Australia (754319). Pending patent in Brazil, Canada, China, Europe, Israel, Japan,  Mexico, and South Korea

Abstract

The invention is a new genotype of wheat with tolerance to the root pathogens Rhizoctonia solani, Rhizoctonia oryzae, Pythium ultimum, and Pythium irregulare group IV.  This genotype was originally generated by screening mutagenized seed of the spring wheat for increased tolerance to Rhizoctonia solani.  Later experiments determined that tolerance is due to a transmissible semi-dominant, single gene trait.  This wheat genotype represents the first case of genetic tolerance to the Rhizoctonia root rot in wheat. 

Rhizoctonia root rot is an important yield-limiting disease in direct-seeded wheat production in the US Pacific Northwest, Canada, and Australia.  Under severe disease pressure, plants are stunted, and seedlings are killed, creating uneven stands and bare patches in the field, which severely reduces grain yields and grain quality.  No fungicide capable of controlling this pathogen is available.  Currently, Rhizoctonia is managed through crop rotation, tillage, or by using glyphosate (Roundup) to eliminate infected plants from the previous crop year (green bridge).  As Rhizoctonia and Pythium exhibit broad host ranges, rotation is less effective compared to other pathogens.  These practices increase reduced profitability, increase the risk of soil loss due to erosion, and increase risk of developing glyphosate tolerant weed populations due to excessive application.  The commercial release of a Rhizoctonia tolerant wheat variety could increase acceptance of reduced tillage/direct-seeded farming systems, thereby decreasing soil erosion, reducing production costs, and increasing profitability.

Applications and Advantages

Offers effective and cost-saving measure to effectively control soilborne pathogens, thereby increasing crop yield and profitability.

IP Status

US and PCT applications pending                 

Publication

PCT publication WO 2007092907

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.       

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.    

IP Status

Patents issued in: US (7,402,417); and several others pending. 

Abstract

Vaccination of pigs against porcine reproductive and respiratory syndrome virus (PRRSV) is the most prudent and logical way of controlling this economically important disease which costs over $600 million annually to the US pork industry. Production of vaccines requires large scale propagation of PRRSV in the laboratories of pharmaceutical companies.  The cell-line that is currently available for propagation of PRRSV in vitro is the green monkey kidney epithelial cell-line (and its derivatives), which has been patented by Boehringer Ingelheim.  Availability of additional cell-lines for propagation of PRRSV should enhance the development of vaccines by several Biologics Companies, which will increase the likelihood of several efficacious vaccines against PRRSV becoming available in the future.

WSU inventors employed transfection techniques to develop macrophage cell-lines suitable for propagation of PRRSV in vitro.  Sialoadhesin has been identified as the receptor for PRRSV om PAMs.  Transfection of porcine sialoadhesin into macrophage cell-lines from other species should render them peremissive for PRRSV replication.  The gene encoding porcine sialoadhesin were then cloned, sequenced, and the transfected it into a mouse macrophage cell-line (J774A.1).  One transfectant was subjected for further studies and found to be permissive for PRRSV replication. PRRSV replicates to a titer of 1x105. 

This WSU transfectant macrophage cell line could then be used for propagation of PRRSV for the development of vaccines against this economically important disease of pigs.

Applications and Advantages

Offers alternative cell culture systems to develop next generation of vaccines against PRRSV

IP Status

US and PCT patent applications pending

Publication

PCT Publication No. WO 2008109237A2

US Publication No. US-2010-0146653-A1

Abstract

This technology relates to a new PCR diagnostic test developed here at WSU for the detection of caulimoviruses. This test is useful for broad spectrum detection of caulimos. Some of the tested members include CaMV, Figwort mosaic virus, Dahlia mosaic virus, carnation etched ring virus, Horseradish latent virus and Mirabilis mosaic virus.

Members of the genus Caulimovirus are characterized by a double-stranded DNA genome of about 8 kb in size and they infect a wide range of crops. Considerable divergence exists in the genomic sequences of these viruses.  As a result, virus-specific probes have to be used for their diagnosis. Tools that could detect a wide range of caulimoviruses in a single test would be rapid and less expensive.  Based on conserved regions of known caulimovirus genomes, degenerate primers were designed and used in a polymerase chain reaction-based assay.  Several members of the genus could be detected using these primers.  The method facilitates rapid diagnosis of caulimoviruses in crops.

Applications and Advantages

Facilitates rapid and economical diagnosis of caulimoviruses in crops

Publication

Pappu, H.R., and K.L Druffel. 2008. A group-PCR assay for the detection of members of the genus Caulimovirus. Annual meeting of the American Phytopathological Society, July 26-30, 2008. Minneapolis, MN. Phytopathology 98 (supplement). http://www.apsnet.org/

Abstract

The technology is related to genes encoding plant acyl-CoA thioesterases from Arabidopsis and methods of their use.  Fatty acids have been extensively exploited for industrial uses in products such as lubricants, plasticizers, and surfactants. In fact, approximately one-third of vegetable oils produced in the world are already used for non-food purposes. Manipulating the genes in the triacylglycerol (TAG) synthesis pathway can contribute to altered or increased fatty acid content in oilseeds.

Most of the efforts to modify TAG content have focused on either increasing the nutritional characteristics and chemical stability of edible oils or on introducing new and unusual fatty acids into TAGs for use in various industrial applications. Progress has been achieved through over-expression and/or suppression of a modestly small number of genes in the TAG synthesis pathway. However, to date, the alterations in fatty acid content have not been substantial enough to create truly meaningful new oilseed lines. Thus, this technology has the potential to increase the TAG content in transgenic crops.

Applications and Advantages

■  Has the potential to develop plants containing specialized fatty acid compositions;

■  Offers to increase the triacylglycerol content in transgenic crops.

IP Status

Patents issued: US (6,878,861); and several others pending. 

Abstract

This invention relates to a peptide signal for inducing plant defense response against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium. There is todate, no direct evidence for the involvement of endogenous peptide signaling in the activation of either local or systemic microbial pathogen defense responses in plants.

WSU inventors have isolated a peptide from Arabidopsis thaliana that acts as a signal for defense against pathogen attacks.

The signal induces the transcription of several known defense genes of Arabidopsis including a defensin gene, a tyrosine amino transferase gene and two PR protein genes, as if the plants were being infected by pathogens. These genes are well characterized genes that are inducible in Arabidopsis leaves in response to pathogen attacks. The gene orthologs have been identified in several other crop plants including rape, soybeans, alfalfa, potato, poplar and rice. These agriculturally important plants are of widely diverse evolutionary origins, indicating that the peptide may be a universal signal in plants for defense against pathogens.

Applications and Advantages

■   Offers a distinct advantage to the plants in mounting resistance responses against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium;

■   Provides a way of constitutively over-expressing natural defense genes, prior to pathogen attacks.

IP Status

US patent application pending

Publication 

Huffaker, Alisa; Ryan, Clarence. 2008. PROPEP Family Regulation of Pathogen Defense in Arabidopsis thaliana. Plant Biology 2008. Organized by the American Society of Plant Biologists. June 26 - Tuesday July 1, Mérida, Mexico

Abstract

Bovine tuberculosis (TB) and Johne’s disease are economically important diseases of ruminants. Bovine tuberculosis is caused by Mycobacterium bovis (Mbv), while Johne’s disease is caused by M. avium subsp. Paratuberculosis (Map.). According to the Agricultural Research Service of the USDA, Johne’s disease costs the U.S. dairy industry about $200 million a year in reduced milk production and there are additional costs due to early culling of animals. Bovine TB, one of three types of TB (human, avian, and bovine), can infect all warmblooded vertebrates. The lack of diagnostic tests to detect infected animals early in the course of disease combined with the lack of effective vaccines make controlling these diseases is difficult.

WSU inventors have adapted and improved an allele exchange technique for creating mutant strains of mycobateria, creating a disruption in a selected gene. This improved efficiency of gene disruption has provided an opportunity to target genes essential for in vivo survival of the bacteria. Specifically, the research team used the technique to successfully develop two mutants for Mbv and three for Map. Studies are currently in progress with the Map mutants to show they elicit protective immunity, which could then be used as vaccines.

Applications and Advantages

Provides opportunity to develop better vaccines and improved diagnostic kits for bovine tuberculosis and John’s disease.

IP Status

US, Mexico and Canada patent applications pending                                         

Publication

PCT Publication No. WO 2009009798

Park, Kun Taek, Dahl, John, Bannantine, John P. , Barletta, Rau´l G. ,  Ahn, Jongsam, Allen, Andrew J. , Hamilton, Mary Jo, and Davis, William. 2008. Demonstration of Allelic Exchange in the Slow-Growing Bacterium Mycobacterium avium subsp. paratuberculosis, and Generation of Mutants with Deletions at the pknG, relA, and lsr2 Loci. Applied and Environmental Microbiology 74(6): 1687-1695

Abstract

An 8 amino acid peptide was isolated from soybean leaves that is capable of alkalinizing the media of soybean suspension cells, a response that is generally associated with defense peptides.  The peptide was found to be active at low concentrations with an extremely fast response time.  The peptide is located on the carboxy-terminal end of a precursor protein deduced from a est library and found to induce defense genes.  This and a homologue were both highly expressed in the roots, relative to the aerial portions of the plant.  Treatment of the aerial portion of soybean plants with hormones involved in elicitation of defense responses revealed a significant increase in expression levels.

Abstract

This invention relates to a peptide signal for inducing plant defense response against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium. There is to date, no direct evidence for the involvement of endogenous peptide signaling in the activation of either local or systemic microbial pathogen defense responses in plants.

WSU inventors have isolated a peptide from Arabidopsis thaliana that acts as a signal for defense against pathogen attacks. The signal induces transcription of several known defense genes of Arabidopsis including a defensin gene, a tyrosine amino transferase gene and two PR protein genes, as if the plants were being infected by pathogens. These genes are well characterized genes that are inducible in Arabidopsis leaves in response to pathogen attacks. The gene orthologs have been identified in several other crop plants including rape, soybeans, alfalfa, potato, poplar and rice. These agriculturally important plants are of widely diverse evolutionary origins, indicating that the peptide may be a universal signal in plants for defense against pathogens.

Applications and Advantages

■  Provides a way of constitutively over-expressing natural defense genes, prior to pathogen attacks;  

■  Provides a distinct advantage to the plants in mounting resistance responses against nectotrophic or saprophytic pathogens such as Alternaria, Botrytis, Septoria, Pythium, Erwina, Plectospphaerella, and Verticillium. 

Publication

Pearce, G., Y. Yamaguchi , G Munske and C.A. Ryan. 2008. Structure-activity studies of AtPep1, a plant peptide signal involved in the innate immune response. Peptides 29: 2083-2089.

Abstract

How carbon flux differentially occurs in vascular plants for protein synthesis, phenylpropanoid metabolism (i.e. lignins) and other metabolic processes is not well understood. Having previously discovered/validated that a six-membered arogenate dehydratase (ADT 1-6) family encodes the final step in Phe biosynthesis in Arabidopsis thaliana, this raised the fascinating question whether individual ADT isoforms (or combinations thereof) differentially modulated carbon flux to lignins, proteins, etc. WSU scientists obtained homozygous T-DNA insertion lines for 5 of the 6 ADTs, these being used to generate double/triple knockouts in all possible combinations. Various mutants gave phenotypes with profound but distinct reductions in lignin amounts and not accompanied by gross anatomical/growth and development defects, such as dwarfing. This is the first example of a plastid-localized metabolic step profoundly affecting carbon flux into lignin.

Applications and Advantages

This invention can facilitate further research, and development to further unravel the complexities of lignin biosynthesis at the cellular and tissue levels. Moreover, this offers opportunity to establish: specific roles of each ADT in various aspects of phenylpropanoid and lignin forming metabolic processes, including detailed metabolomic analyses, and a new means to probe lignin primary structure as well as the physiological consequences of lignin deposition reduction. Potential applications include controlling lignin flux where increased lignin can be exploited for production of commercially valuable compounds while decreased lignin can be exploited in the field of bioenergy.

IP Status

US provisional patent application pending

Publication

Man-Ho Cho, Oliver R. A. Corea, Hong Yang, Diana L. Bedgar, Dhrubojyoti D. Laskar, Aldwin M. Anterola, Frances Anne Moog-Anterola, Rebecca L. Hood, Susanne E. Kohalmi, Mark A. Bernards, ChulHee Kang, Laurence B. Davin, and Norman G. Lewis. Phenylalanine Biosynthesis in Arabidopsis thaliana. Identification and Characterization of Arogenate Dehydratases. The Journal of Biological Chemistry. 2007, 282 (42), 30827-30835

Abstract

Brassinosteroids are plant-specific steroid hormones and are known to play an important role in coupling environmental factors, especially light, with plant growth and development.  Ca²⁺/calmodulin plays an essential role in sensing and transducing environmental stimuli. Arabidopsis DWARF1 (DWF1) is responsible for an early step in brassinosteroid biosynthesis that converts 24-methylenecholesterol to campesterol. 

WSU inventors discovered that DWF1 is a Ca²⁺/calmodulin-binding protein and this binding is critical for its function.  Our inventors showed that loss of calmodulin-binding totally abolished the function of DWF1 in planta, while partial loss of calmodulin-binding resulted in a partial dwarf phenotype in complementation studies.  These results provide direct proof that Ca²⁺/calmodulin-mediated signaling plays a critical role in controlling the function of DWF1 which could be used to producing size-engineered crops by altering the Ca²⁺/calmodulin-binding property of their DWF1 orthologs. DWF1 orthologs from other plants have a similar Ca²⁺/calmodulin-binding domain, implying that Ca²⁺/calmodulin regulation of DWF1 and its homologs is common in plants.

Applications and Advantages

The discovery by WSU scientists provides a new biotechnological approach to produce semi-dwarf or size-engineered plants. This approach is applicable to a wide range of plants, and is valuable for crop breeders.

IP Status

US patent application pending.                    

Publication

Du, L. and Poovaiah, BW. 2005. Ca²⁺/calmodulin is critical for brassinosteroid biosynthesis and plant growth. Nature 437(7059):741-745.

US Patent Publication No. US20070089183A1

Abstract

Intracellular calcium transients during plant-pathogen interactions are necessary early events leading to local and systemic acquired resistance. Salicylic acid, a critical messenger, is also required for both these responses,  but whether and how salicylic acid level is regulated by Ca2+ signaling during plant-pathogen interaction is unclear.  Here a novel mechanism connecting Ca2+ signal to salicylic acid-mediated immune response through calmodulin, AtSR1/CAMTA3, a Ca2+/calmodulin-binding transcription factor, and EDS1, an established regulator of salicylic acid level, is reported.  Constitutive disease resistance and elevated levels of salicylic acid in loss-of-function alleles of AtSR1/CAMTA3 suggest that AtSR1 is a negative regulator of plant immunity.  This was confirmed by epistasis analysis with mutants of compromised salicylic acid accumulation and disease resistance.  This WSU research shows that AtSR1 interacts with the promoter of EDS1 and represses its expression.  Furthermore, Ca2+/calmodulin-binding to AtSR1 is required for suppression of plant defense, indicating a direct role for Ca2+/calmodulin in regulating the function of AtSR1.  These results revealed a novel regulatory mechanism linking Ca2+ signaling to salicylic acid level.

IP Status

US patent application filed

Publication(s)

US patent pub No. US-2010-0223690-A1

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.

IP Status

Patent pending in US.                 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages 

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.  

IP Status

Patents issued in: US (6,114,160; 6,610,527)

Abstract

WSU scientists have recently unveiled the previously unknown regulatory mechanism linking calcium signaling to salicylic-acid-mediated responses, both implicated for regulating plant disease-resistance response. Working on a model plant Arabidopsis thaliana, they showed that AtSR1 (Arabidopsis thaliana signal responsive 1), a calcium/calmodulin-binding transcription factor, is a negative regulator of plant immunity since it suppresses the biosynthesis of salicylic acid, a hormone that promotes disease resistance. Plants with loss-of-function alleles of AtSR1 have elevated expression of genes associated with systemic acquired resistance and displayed enhanced resistance to pathogens such as Pseudomonas syringae. They discovered that these changes coincide with increased production of salicylic acid and that the repression of the immune response by AtSR1 is regulated by calcium/calmodulin.

The constitutive loss of AtSR1 has enhanced plant disease reistance yet resulted in reduced plant growth, which is not advantageous for commercial applications. To overcome this, the same group of WSU scientists has conditionally reduced the function of AtSR1 using an inducible promoter-driven antisense or RNAi (RNA interference) construct of AtsR1. Crops transformed using the RNAi construct resulted in a stable modification of the biochemical pathway, resulting in disease-resistant phenotypes without affecting plant growth.

Applications and Advantages

The invention offers to revolutionize breeding programs focused on disease resistance without sacrificing growth and yield for almost every agronomic crop. It can also facilitate research, development, and expansion of the use of RNAi technology for determining other function of genes related to disease resistance and other stress-related traits.

IP Status

Available for licensing

Abstract

Improvements in plant productivity (biomass) and yield have centered on increasing the efficiency of leaf carbon dioxide fixation and utilization by non-photosynthetic sink organs. This technology focuses on exploiting leaf starch synthesis as a transient sink to increase plant productivity and yields. In particular, transgenic Arabidopsis were used as examples where mutant transgenic plants were shown to exhibit enhanced photosynthetic capacity that translated into increased growth and biomass.  

Applications and Advantages

• Offers a viable alternative strategy to increase productivity and yields of crop and bio-energy plants.

IP Status

US provisional patent

Abstract

Our research team has demonstrated that recombinant protein can be synthesized and secreted directly into the supernatant. The novelty of this invention is that the 5’ end of potentially any Type III secreted protein can be used to drive the export of a recombinant protein from a bacterial cell. Likewise, although this platform was tested for Campylobacter, the technology is versatile enough to be used for: a) production of other vaccines; and b) enable expression of difficult-to-express proteins because of cell toxicity type issues. In this latter case, the expression is facilitated because of the system’s ability to shunt proteins into the supernatant and not retain them within the cell.  This feature makes it easier also to purify the expressed protein.

Applications and Advantages

Offers a versatile method enough to be used for (a) production of other vaccines; and (b) expressing difficult-to-express proteins because of cell toxicity type issues

IP Status  

US patent application pending

Publication(s)

Neal-McKinney, J.M., Christensen, J.E., and M.E. Konkel. 2010. Amino-terminal residues dictate the export efficiency of the Campylobacter jejuni filament proteins via the flagellum. Molecular Microbiology. Mol Microbiol. 76(4). 918-931

Christensen, J.E., Pacheco, S.A., and M.E. Konkel. 2009.Identification of a Campylobacter jejuni-secreted protein required for maximal invasion of host cells. Mol Microbiol 73(4). 650-662

Abstract

This technology utilizes novel probes to detect and identify target biomolecules in a sample. These probes employ conformational changes induced by molecular recognition events to initiate changes in the optical properties of the probe (e.g. the modulation of a fluorescence or absorption response upon target binding). Methods, including solid phase synthesis techniques for making probe molecules have been developed.

Applications and Advantages

■  Versatile approach to molecular recognition

■  Hairpin formation not a prerequisite for self association

■  Optical response can be tailored to application

■  Multiple targets can be probed simultaneously

■  Both the composition and nature of the probes and reporters can be modulated

IP Status 

US Patent Nos. 7,238,792; 7,556,967

Publications

Han, Jason J.; Wang, Wei; Li, Alexander D. Q.. Folding and Unfolding of Chromophoric Foldamers Show Unusual Colorful Single Molecule Spectral Dynamics. Journal of the American Chemical Society (2006), 128(3), 672-673.

Wang, Wei; Wan, Wei; Stachiw, Andrew; Li, Alexander D. Q.. Foldamers with Hybrid Biological and Synthetic Sequences as Selective DNA Fluorescent Probes. Biochemistry (2005), 44(32), 10751-10756.

Wang, Wei; Wan, Wei; Zhou, Hong-Hui; Niu, Shuqiang; Li, Alexander D. Q.Alternating DNA and ï° -conjugated sequences. Thermophilic foldable polymers. Journal of the American Chemical Society (2003), 125(18),5248-5249.

Wang, Wei; Li, Lin-Song; Helms, Greg; Zhou, Hong-Hui; Li, Alexander D. Q.. To Fold or to Assemble? Journal of the American Chemical Society (2003), 125(5), 1120-1121.

Abstract

This invention relates to methods to engineer biomimetic vectors with chimeric architecture for targeted gene therapy. WSU inventor has engineered a multi-domain biomacromolecule using a novel technique and identified the structure of a vector where the functional propensity of the concept biomacromolecule is scripted into the primary sequence structure to perform an array of self-guided functions. These include: a) efficient condensation of the plasmid DNA into deliverable nanoparticles by adenovirus mu peptide, b) delivery of the nanoparticles to model breast cancer cells using a combinatorially screened cyclic targeting peptide (TP) [1], c) endosomal disruption using a synthetic fusogenic peptide (FP) facilitating escape of the cargo into cytosol, and finally d) localization of the gene in the nucleus by HIV nuclear localization signal (NLS). By shuffling the order of the functional domains, a library of the DNA transporters was genetically engineered to screen the active candidate with the optimum sequence for a purpose. This method/technique is applicable to any type of molecule (DNA/peptide/RNA/siRNA, etc. ) with any number of elements in the vector and can be adapted to many purposes.

Applications and Advantages

Offers a biomimetic vector for efficient and targeted gene transfer.

IP Status 

US patent application pending

Publications

B.F. Canine, Y. Wang, A. Hatefi. 2009. Biosynthesis and characterization of a novel genetically engineered polymer for targeted gene transfer to cancer cells. J Control Release  138(3) : pp 188-196

S.S. Mangipudi, B.F. Canine, Y. Wang, A. Hatefi. 2009. Development of a Genetically Engineered Biomimetic Vector for Targeted Gene Transfer to Breast Cancer Cells. Mol. Pharmaceutics 6 (4): 1100–1109 .

Y. Wang, S.S. Mangipudi, B.F. Canine, A. Hatefi. 2009. A designer biomimetic vector with a chimeric architecture for targeted gene transfer. J Control Release  137(1): 46-63

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.

IP Status  

Patents issued in: US (6,610,527; 5,994,114);  France, Europe, United Kingdom, Switzerland, and Spain (0907312); Italy (26217/BE/2006);  Germany (DE 69735419) ; Canada (2,250,693) ; Australia (710405)

Several others pending.   

Publications

Jennewin, Stefan; Rithner, Christopher; Willliams, Robert; and Croteau, Rodney. Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase. PNAS (2001), 98(24), 13595-13600

Jennewein, Stefan; Wildung, Mark; Chau Mydoanh; walker, Kevin, and Croteau, Rodney. Random sequencing of an induced Taxus cell cDNA library for identification of clones involved in Taxol biosynthesis . PNAS (2004), 101(24), 9149-9154 .

Abstract

Among the arsenal of plant-derived compounds activated upon attack by herbivores and pathogens are small peptides that initiate and amplify defense responses. However, only a handful of plant signaling peptides have been reported.  WSU inventors have isolated a 12 amino acid peptide from soybean (Glycine max) leaves which causes a pH increase of soybean suspension-cultured cell media within 10 min at low nanomolar concentrations, a response that is typical of other endogenous peptide elicitors and pathogen-derived elicitors. The amino acid sequence was determined and a synthetic peptide, when supplied to soybean cultures, induced the expression of known defense-related genes.

Applications and Advantages

This invention presents exciting new possibilities for understanding basic mechanisms of plant protection. The uniqueness of the nucleotide sequence may provide a site for genetic manipulation for expressing other defense peptides.

IP Status

US patent application pending

Abstract

Grapevine leafroll disease (GLRD) is an economically important virus disease to the sustainability of the grape and wine industry in Washington State.  An infectious cDNA clone (GLRaV-3) that has been developed by WSU researchers will help apply reverse genetics to study the molecular biology of grapevine-infecting closteroviruses and the etiology of GLRD.  The cDNA clone has the potential to be used as a vector to express foreign genes and heterologous proteins in grapevine and is amenable for use as a vector for studies on virus-induced gene silensing (VIGS) in grapevine.

The cDNA clone is the most prevalent worldwide among all GLRaVs and can be spread by insect vectors like mealybugs and scale insects.  The clone is taxonomically aligned more closely with other GLRaVs (genus Ampelovirus, family Closteroviridae) and is the type member of the genus Ampelovirus, which includes viruses causing serious diseases in other agriculturally important perennial crops like pineapple (Pineapple Mealybug Wilt-associated Virus 1), cherries (Little Cherry Virus 2) and plums (Plum Bark Necrosis Stem Pitting-associated Virus). The clone's vector system would provide basic knowledge that has potential practical value to similar viruses infecting other perennial fruit crops.

IP Status

Available for licensing  

Abstract

These WSU technologies relate to reducing the incidence of C. jejuni bacteria infections in poultry and in humans, and more particularly to novel antigenic 5 compositions, vaccines, and methods for generating an immune response against C. jejuni bacteria in an animal.

Our research team has identified 30 “best-fit” antigenic composition or immunogenic membrane-associated C. jejuni proteins. These antigenic compositions are potentially valuable vaccine candidates that can be orally administered through the bird’s water or food supply. In research trials, these antigenic compositions have significantly reduced the pathogen's ability to colonize young chickens' intestines, where the infection begins. These technologies and methods could provide an effective alternative to antibiotics the poultry industry uses to control these pathogenic bacteria.

The methods developed for Campylobacter are, however, versatile enough to be used for (a) production of other vaccines; and (b) expressing difficult-to-express proteins because of cell toxicity type issues. In this latter case, the expression is facilitated because of the system’s ability to shunt proteins into the supernatant and not retain them within the cell.  This feature makes it easier also to purify the expressed protein.

Campylobacter jejuni is now the No. 1 food-borne pathogen in the United States and the world, surpassing Salmonella. In the United States alone, 2.4 million cases are reported annually, with with an estimated cost of treatment and loss of productivity of $8 billion annually. Humans are frequently infected with C. jejuni by handling or consuming raw poultry products. 

Applications and Advantages

Offers novel vaccine candidates and methods to generate immune response against Campylobacter jejuni in chickens, and other avian species.

IP Status 

US patent application pending

Publication                          

Shoaf-Sweeney, K.D., Larson, C.L., Tang, X., and M.E. Konkel. Identification of Campylobacter jejuni proteins recognized by chicken maternal antibodies.  Appl. Environ. Microbiol. 74:6867-6875, 2008

Konkel, M.E., Larson, C.L., and R.C. Flanagan. The food-borne pathogen Campylobacter jejuni synthesizes a novel fibronectin-binding protein termed FlpA that facilitates adherence to human epithelial cells. J. Bacteriol. 192:68-76, 2010.

Flanagan, R.C., Neal-McKinney, J.M., Dhillon, A.S., Miller, W.G., and M.E. Konkel.  Examination of Campylobacter jejuni putative adhesins leads to the identification of a new protein, designated FlpA, required for chicken colonization.Infection and Immunity. 77(6):2399-407, 2009 

Abstract

This technology is a new method of transforming cereals for transferring desirable genes.  This method involves dipping spikes of cereals into Agrobacterium harboring the plasmid and gene of interest.  The production of transgenic seed can be achieved in 3 months. The use of Agrobacterium allows for single or low copy gene insertion.  This involved determining the best Agrobacterium strain, the genotype most amenable to transformation, changing the infiltration media, and determining the optimal age of transformation.

Applications and Advantages

■  Offers a new, faster and cheaper method of transforming cereals to enable transfer of desirable genes;

■  Offers to address issues of multiple genes insertions and subsequent gene silencing, all problems associated when using biolistics.

IP Status

US patent application pending 

Publication

Zale, J., Agarwal, S., Loar, S., Steber, C.M. 2009. Evidence for stable transformation of wheat by floraldip in Agrobacterium tumefaciens. Plant Cell Reports 28(6):903-913.                  

Abstract

Mannheimia (Pasteurella) haemolytica is the most important bacterial pathogen of respiratory disease in cattle, sheep, and other domestic and wild ruminants. This bacterial pathogen produces leukotoxin, which kills the white blood cells, and, hence is primarily responsible for bronchopneumonia and death in ruminants. Pneumonic diseases cause huge economic losses to the cattle and sheep industries worldwide.

WSU has a strong research program focused on understanding the pathogenesis of animal diseases such as pneumonia caused by M. haemolytica and developing effective and cost-efficient control and preventive measures against this pathogen.  A team of WSU veterinary microbiologists and pathologists recently found that the growth and colonization of the M. haemolytica can be inhibited using another bacterial species by a contact dependent mechanism, a phenomenon recently found among Escherichia coli strains. This team had isolated leukotoxin-negative Bibersteinia trehalosi(inhibitor) to inhibit the growth of M. haemolytica (target). B. trehalosiis also one of the most common bacterial isolates that cause pulmonary diseases in ruminants (especially in big sheep horns), with only 15 percent of the strains producing leukotoxin. Although the two bacterial species are closely related on the family tree and cultured in close proximity to each other, studies by WSU experts showed that “horizontal gene transfer” did not happen, hence, the isolated B. trehalosi strains are free of leukotoxin gene found in M. haemolytica.

Applications and Advantages

The isolated B. trehalosi strains can be used as nasal spray to eliminate M. haemolytica that are present as commensal bacteria in the nasopharynx of cattle, domestic sheep and other ruminants.

IP Status

Available for licensing

Abstract

WSU pioneered another research focused on a genome-wide association study to identify loci putatively associated with tolerance to bovine tuberculosis, an economically important infectious disease in cattle. Bovine paratuberculosis, commonly referred to as Johne's disease, is a contagious bacterial disease estimated to be present in over 65% of US dairy herds and results in annual losses in the hundreds of millions of US dollars. Mycobacterium avium subspecies paratuberculosis (MAP) is the bacteria responsible for Johne's disease. 

WSU researchers did the whole genome association analysis using BovineSNP50 BeadChip, and identified multiple single nucleotide polymorphisms (SNPs) associated with Johne's disease after stringent multiple testing correction. The SNPs identified as being associated with tolerance to/infection with MAP included previously unreported regions on chromosome 1 and the X chromosome.

Tolerance, which indicates the fitness of the hosts at a given level of tissue infection, represents a new way of evaluating the impact of disease on animals and a new means of marker assisted selection for carcass and health traits in cattle.  Selection of animals for tolerance would put different pressures on the host (cattle) and the pathogen (MAP) and can be an effective means of controlling this disease than selection for disease resistance.

Applications and Advantages

■   Selection of tolerant animals that are less harmed by MAP infection, reducing the transmission of MAP to other animals in the herd, and improving profitability in cattle.

IP Status

US patent application filed

Publication

R. Zanella,  M. L. Settles, S. D. McKay, R. Schnabel,  J. Taylor, R. H. Whitlock, Y. Schukken, J. S. Van Kessel,  J. M. Smith, H. L. Neibergs. 2010. Identification of Loci Associated with Tolerance to Johne’s Disease in Holstein Cattle. Animal Genetics. pp  1- 11.

US-2010-0223687-A1

Abstract

WSU pioneered another research focused on a genome-wide association study to identify loci putatively associated with tolerance to bovine tuberculosis, an economically important infectious disease in cattle. Bovine paratuberculosis, commonly referred to as Johne's disease, is a contagious bacterial disease estimated to be present in over 65% of US dairy herds and results in annual losses in the hundreds of millions of US dollars. Mycobacterium avium subspecies paratuberculosis (MAP) is the bacteria responsible for Johne's disease. 

WSU researchers did the whole genome association analysis using BovineSNP50 BeadChip, and identified multiple single nucleotide polymorphisms (SNPs) associated with Johne's disease after stringent multiple testing correction. The SNPs identified as being associated with tolerance to/infection with MAP included previously unreported regions on chromosome 1 and the X chromosome.

Tolerance, which indicates the fitness of the hosts at a given level of tissue infection, represents a new way of evaluating the impact of disease on animals and a new means of marker assisted selection for carcass and health traits in cattle.  Selection of animals for tolerance would put different pressures on the host (cattle) and the pathogen (MAP) and can be an effective means of controlling this disease than selection for disease resistance.

Applications and Advantages

■   Selection of tolerant animals that are less harmed by Map infection, reducing the transmission of Map to other animals in the herd, and improving profitability in cattle.

IP Status

US patent application filed

Publication

R. Zanella,  M. L. Settles, S. D. McKay, R. Schnabel,  J. Taylor, R. H. Whitlock, Y. Schukken, J. S. Van Kessel,  J. M. Smith, H. L. Neibergs. 2010. Identification of Loci Associated with Tolerance to Johne’s Disease in Holstein Cattle. Animal Genetics. pp  1- 11

US-2010-0223687-A1

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/ lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants: enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,635,459; 6,210,942), Australia (728116) and several others pending. 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.                                                                  

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production. 

Abstract

This technology relates to the utility of using RT-PCR technique to detect whether or not climacteric fruit have been subjected to treatment with a commercial inhibitor of ripening. 1-MCP, the inhibitor, is effective as a gas treatment at levels of 1ppm or lower and does not leave detectable residue on the produce while fostering somewhat dramatic effects on the progression of ripening, hence deterioration of fruits that require ethylene gas, a naturally-occurring plant hormone, to initiate the onset of ripening.  Fruits that require ethylene synthesis and perception to ripen are termed climacteric fruits.  Upon ethylene perception, a cascade of biochemical changes associated with the ripening process proceeds, resulting in a ripened commodity with optimal fresh eating quality.  By use of specific primers for ripening-associated gene expression, 1-MCP treatment is easily detectable using RNA extracted from the fruit.

Applications and Advantages

Use of reverse-transcriptase polymerase chain reaction (RT-PCR) offers rapid detection and quantification whether or not climacteric fruit have been subjected to treatment with ripening inhibitors such as 1-methylcyclopropene (MCP), an ethylene perception inhibitor.

Abstract

The technology is related to genes encoding plant acyl-CoA synthetases (ACS) from Arabidopsis and methods of their use. Fatty acids have been extensively exploited for industrial uses in products such as lubricants, plasticizers, and surfactants. In fact, approximately one-third of vegetable oils produced in the world are already used for non-food purposes. Manipulating the genes in the triacylglycerol (TAG) synthesis pathway can contribute to altered or increased fatty acid content in oilseeds.

Most of the efforts to modify TAG content have focused on either increasing the nutritional characteristics and chemical stability of edible oils or on introducing new and unusual fatty acids into TAGs for use in various industrial applications. Progress has been achieved through over-expression and/or suppression of a modestly small number of genes in the TAG synthesis pathway. However, to date, the alterations in fatty acid content have not been substantial enough to create truly meaningful new oilseed lines. Thus, this technology has the potential to increase the TAG content in transgenic crops.    

Applications and Advantages

■  Has the potential to develop plants containing specialized fatty acid compositions;

■  Has the potential to increase the triacylglycerol content in transgenic crops.      

IP Status

Patents issued in: US (7,105,722); and several others pending. 

Abstract

After nearly a decade of research, WSU scientists have discovered new ways to trigger quicker response and elucidate defense mechanisms of plants against stem rust, and potentially to defeat the deadly wheat steam rust race TTKSK (also known as Ug99). Stem rust, caused by the fungus Puccinia graminis (P. graminis), is a virulent disease that can destroy a grower's entire crop and affects wheat, barley, rye, and others. The recent appearance of its new strain Ug99 poses further threats to the cereal industry worldwide.

Our researchers worked on the barley stem rust R gene, Rpg1 (Reaction to P. graminis 1), which provides durable resistance to the stem rust pathogen P. graminis f. sp. tritici, a trait highly desirable and very relevant to barley and wheat breeding. Their recent in vivo findings revealed that the combined action of two avirulent spore effectors applied on the leaf surface of the barley plant works to activate plant defenses (as quick as 5 min) prior to pathogens arrival. This results to enhanced ability of the plant to fight off stem rust infection before it even starts. Concerted action of both identified proteins from stem rust pathogens triggered rapid phosphorylation and eventual degradation of Rpg1. The process initiates resistance to stem rust on the susceptible cultivar. These are breakthroughs that can revolutionize the fight against rust affecting cereal grains.

Applications and Advantages

The effects of Rpg1 and the discovery of the proteins that activate Rpg1-mediated resistance stem rust, together with the simple means of application (e.g. spray application) provide a strong basis for investment and commercialization of this WSU technology.

IP Status

Under review

Abstract

     Harmful strains of Eschiricia coli bacteria, primarily found in cattle cause severe, sometimes life-threatening human illness. According to the US’ Centers for Disease Control and Prevention, an estimated 110,000 cases (due to specifically enterohaemorrhagic E. coli (EHEC)) occur annually in the United States, and is now plaguing more than 30 countries around the globe. The other E. coli virotype, enterotoxigenic E. coli (ETEC), according to the World Health Organization, causes more than 200 million cases of diarrhea and 380,000 deaths, mostly in children in developing countries.

     Typically, growth and division of these bacteria are inhibited using antibiotic drugs, which interfere with bacterial metabolic processes. Heavy use of antibiotics, however, resulted to drug-resistant forms of E. coli. Bacterial contact inhibition offers new way to interfere with bacterial growth and growth arrest. Current contact-dependent inhibition mechanisms, however, have a narrow target range. More importantly, the route of infection to humans is via contaminated meat where there is a zero tolerance policy in place. This in turn necessitates removal of the harmful bacteria before cattle enter the slaughterhouse.

     A team of WSU veterinary microbiologists and pathologists have discovered a novel inhibition mechanism that is effective against diverse panel of E. coli, including E. coli O157:H7 and can be exploited to further control or prevent colonization of cattle by E.coli virotypes in humans, livestock, and poultry. The team has identified a proximity-dependent inhibition phenotype of E.coli, expressed when E-coli strains are co-cultured in defined minimal media. The inhibitory activity was specifically found effective against 13 diverse panel of E.coli strains, including EHEC, ETEC, multi-drug resistant and commensal E.coli, among a few. The strains expressing the inhibitory phenotype are likewise immune to inhibition by other inhibitor strains.

Applications and Advantages

■  The effectiveness of our inhibitory mechanism offers great potential for dipstick type application to cattle prior to their entry into slaughterhouse.

■  Discovery is novel and unique from all recognized contact-based inhibition mechanisms; and

■  Inhibition mechanism has broad spectrum activity that includes E. coli strains pathogenic to both humans and animals and shows reduction by at least five logs.

IP status

Available for licensing

Publication

Sawant, A., Casavant, N. C., Call, D., & Besser, T. (2011). Identification and Characterization of Proximity-Dependent Inhibition in Eschirichia coli Isolated from Cattle. Applied and Environmental Microbiology, 2345-2351.

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.         

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants:    enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,210,942; 6,635,459) and several others pending.           

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants:  enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,911,330); New Zealand (508270) and several others pending. 

Abstract

This technology relates to the production of ricinoleic acid using transgenic technology. Ricinoleic acid is a hydroxylated fatty acid with great value as a petrochemical replacement in a variety of industrial processes. Its derivatives are found in products such as dyes, lubricants, nylon, soaps, inks, adhesives, and biodiesel. Current production of ricinoleic acid is worth over $100 million per year. The main commercial source of ricinoleic acid is the seeds of castor bean. However, castor is poorly suited to large-scale agricultural production. Also, the seeds of castor contain ricin, a highly poisonous protein, and produces allergenic proteins causing medicinal problems for workers cultivating and harvesting these plants. It is, therefore, desirable to develop a method that is better suited for large-scale agricultural production of ricinoleate-rich oils using other commodity crops (e.g. soybean or canola) that is less health-risk.

Two important genes have been identified in the pathway of ricinoleic acid metabolism found to provide enhanced production of ricinoleic acid in plants. One of these two genes increased the production of ricinoleic acid by up to 80%, to a total of 30% hydroxy fatty acids in the seed oil of transgenic Arabidopsis. Combining both genes to maximize the production of ricinoleic acid in crop plants are expected to increase production.

Applications and Advantages

■  Has a significant potential advantage over the traditional methods of processing castor bean as well as increasing the much needed supply of ricinoleic acid.

■  Offers to eliminate processing barriers associated with castor bean hence results to better quality ricinoleic acid

IP Status

US, Europe, and PCT applications pending 

Publication

Lu, C., Fulda, M., Wallis, J.G. and Browse, J. 2005 A High-Throughput Screen for Genes from Castor that Boost Hydroxy Fatty Acid Accumulation in Seed Oils of Transgenic Arabidopsis. Plant J. 45:847-856.

Abstract

The present invention relates to nucleic acid sequences which encode polypeptides having PhzO activity, namely, the ability to convert phenazine-1-carboxylic acid to 2-hydroxylated phenazines and isolated polypeptides having this activity.  The invention also relates to recombinant nucleic acid molecules, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing and using polypeptides, including expression in bacterial or plant cells to inhibit fungal pathogens.

Applications and Advantages

The use of the nucleic acid sequences are instrumental for the isolation of homologous genes from microorganisms to obtain genes which protect host cells, including bacteria, and plants against fungal pathogens.

IP Status 

US Patent 6,737,260; 7,189,547

Abstract

This technology relates to new diagnostic tests for the detection of Barley Yellow Dwarf Virus (BYDV). BYDV is an important pathogen of wheat, barley, corn, and oats.  The virus exists as several serotypes such as RPV, RMV, PAV, and SGV.  There are no rapid and sensitive methods for simultaneous detection of these serotypes.  WSU inventors have identified conserved regions within the RNA genomes of these serotypes and designed primers and developed an RT-PCR assay that can detect several serotypes in a single RT-PCR reaction.  A group test for these serotypes is now possible using standard RT-PCR or real-time PCR. Recombinant coat protein from BYDV was used to produce antisera for utilization in an ELISA-based assay and/or an immune-oblot assay for broad spectrum and specific detection of BYDV serotypes.

Applications and Advantages

■    Useful for broad spectrum detection of the c=virus in several crops.

Abstract

This invention utilizes SiRNAs that target mRNA transcripts to down-regulate the expression of peptide products encoded by the preproghrelin gene.  Further information about the effects of the decreased gene expression enables the better understanding of the physiological role of preproghrelin gene products, ghrelin and obestatin, in the regulation of food intake, body weight, thermo-, and sleep regulation.  Previous studies showed that ghrelin is involved in the short- and long-term regulation of energy balance by stimulating feeding and suppressing energy expenditure while obestatin suppresses food intake and body weight gain in mice.  Ghrelin and obestatin are also implicated in sleep regulation.  Sleep deprivation induces increases in hypothalamic and plasma ghrelin levels.  In rats, administration of ghrelin facilitates wakefulness whereas injection of obestatin promotes sleep.

Using transgenic mice as models, WSU inventors characterized sleep and thermo-regulatory responses to food deprivation in cold environment of mice lacking the preproghrelin gene and in a separate experiment, in mice that lack functional ghrelin receptors. Following were the results of our experiments:

1.    Normal mice when exposed to food deprivation at low ambient temperature generated hypothermic bouts (1-5°C decrease in body temperature) accompanied by characteristics metabolic and sleep-wake activity changes.

2.    Mice lacking the preproghrelin gene showed increased sensitivity to the same metabolic challenge.  These mice first entered mild hypothermic bouts, associated with severely reduced sleep which followed by a marked drop in body temperature to near ambient temperature levels.

3.    Mice that lack functional ghrelin receptors showed responses similar to those observed in normal mice when challenged by the same conditions.

4.    Products of the preproghrelin gene are required for maintaining the normal sensitivity to metabolic challenges and coordinated regulation of metabolism and sleep in mice.

Our data provide further insight into the coordinated regulation of metabolism, thermoregulation and sleep.  Regulated hypothermia can be utilized to decrease metabolism during prolonged surgeries, preserve organs before transplantation and also to improve survival of humans during trauma. This research also has high potentials for developing preventive/therapeutic agents for obesity in humans. For example, SiRNAs that inhibit the transcription of the peptide products encoded by the preproghrelin gene or ghrelin antagonists may facilitate weight loss, decrease appetite and to help maintaining normal body weight.  Additional research, however, is needed to realize these objectives.

Applications and Advantages

Have applications in body temperature control and also in the area of obesity  using siRNAs, peptides, etc.

IP Status 

US patent application pending

Publications

US Patent App No. US-2010-0196396-A1

Eva Szentirmai, Levente Kapas, Yuxiang Sun, Roy G. Smith, and James M. Krueger. 2007. Spontaneous sleep and homeostatic sleep regulation in ghrelin knockout mice. Am J Physiol Regul Integr Comp Physiol 293: R510–R517,

Eva Szentirmai, Levente Kapas, and James M. Krueger. 2007. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats Am J Physiol Regul Integr Comp Physiol 292: R575–R585.

Eva Szentirmai, Levente Kapas, Yuxiang Sun, Roy G. Smith,and James M. Krueger. 2009. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. PNAS 106 ( 33): 14069–14074

Abstract

Camelina is one of the crops that is being actively explored and researched in recent days for its potential use as a biofuel crop. Value-added traits that would reduce input costs should aid in exploiting this crop as an alternative fuel crop. This particular technology relates to the use of Arabidopsis/Camelina derived AHL genes and gene products for modulation of cell growth in plants. Our WSU investigators have discovered that mutations within the A-T hook domain confer a dominant negative phenotype to the plants resulting in longer hypocotyls and taller seedlings. 

The practical utility of this discovery is that Camelina can be planted deeper enabling the growing seed to tap into deeper water sources.  This should make it particularly attractive and useful in dryland agriculture. In addition to its utility in Camelina, the mutants can be exploited in other crops of commercial value.

Applications and Advantages

Offers to transform the oilseed, camelina as a better biofuel crop using transgenic technology

IP Status 

US patent application pending

Publication 

Street IH, Shah PK, Smith AM, Avery N, and Neff MM (2008). The AT-hook containing proteins SOB3/AHL29 and ESC/AHL27 are negative modulators of hypocotyl growth in Arabidopsis. Plant Journal 54. 1-14.

Abstract

M. haemolytica is the most important bacterial pathogen of respiratory disease in cattle and other domestic and wild ruminants. This disease, commonly known as pneumonic pasteurellosis or shipping fever in cattle, has been estimated to cost  US $1 billion to the cattle industry of the United States alone. Leukotoxin (Lkt)-induced polymorphonuclear leukocytes (PMN) lysis and degranulation are the primary causes of acute inflammation and lung injury characteristic of pneumonic pasteurellosis.

WSU research team previously identified β₂ integrins as the receptor for Lkt on bovine leukocytes. Subsequently, they have also discovered that Lkt uses CD18 as its receptor on the leukocytes of domestic sheep and bighorn sheep which are also susceptible to pneumonia caused by M. haemolytica. The Lkt binding domain was found to lie between amino acids 1-291 of the CD18 molecule of bovine leukocytes. Based on this amino-acid sequence, synthetic peptides have been developed that effectively inhibit Lkt-induced cytolosis of neutrophils and other leukocytes of cattle. Inhibition of Lkt- induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino-acids 5-17 of CD189, which, surprisingly, comprise most of the amino acids of the signal peptide that remains intact on mature CD18 molecules on the cell surface. The failure of the signal peptide to be cleaved from mature CD18 molecules renders the ruminant leukocytes susceptible to Lkt. These important discoveries, therefore, would enable the cloning of domestic and wild ruminants resistant or much less suceptoble to the lethal effects of pneumonic pasteurollosis thus preventing concomitant economic losses.

Applications and Advantages

Offers the precise binding site of leukotoxin, the most important virulence factor produced by Mannheimia haemolytica on its leukocyte receptor bovine CD18. This finding lends itself to creating vaccines for shipping fever as well as cloning cattle that are resistant to Mannheimia haemolytica.

IP Status 

US and PCT applications pending    

Publication

Shanthalingam, Sudarvili and Srikumaran, Subramaniam. 2009. Intact signal peptide of CD18, the β-subunit of β₂-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin. PNAS 106 (36): 15448-15453

Abstract

M. haemolytica is the most important bacterial pathogen of respiratory disease in cattle and other domestic and wild ruminants. This disease, commonly known as pneumonic pasteurellosis or shipping fever in cattle, has been estimated to cost  US $1 billion to the cattle industry of the United States alone. Leukotoxin (Lkt)-induced polymorphonuclear leukocytes (PMN) lysis and degranulation are the primary causes of acute inflammation and lung injury characteristic of pneumonic pasteurellosis.

WSU research team previously identified β₂ integrins as the receptor for Lkt on bovine leukocytes. Subsequently, they have also discovered that Lkt uses CD18 as its receptor on the leukocytes of domestic sheep and bighorn sheep which are also susceptible to pneumonia caused by M. haemolytica. The Lkt binding domain was found to lie between amino acids 1-291 of the CD18 molecule of bovine leukocytes. Based on this amino-acid sequence of the Lkt-binding domain on CD18, synthetic peptides have been developed that effectively inhibit Lkt-induced cytolosis of neutrophils and other leukocytes of cattle. Inhibition of Lkt- induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino-acids 5-17 of CD189, which, surprisingly, comprise most of the amino acids of the signal peptide that remains intact on mature CD18 molecules on the cell surface. The failure of the signal peptide to be cleaved from mature CD18 molecules renders the ruminant leukocytes susceptible to Lkt. These important discoveries, therefore, would enable the cloning of domestic and wild ruminants resistant or much less susceptible to the lethal effects of pneumonic pasteurollosis, thus, preventing concomitant economic losses.

Applications and Advantages

Offers the precise binding site of leukotoxin, the most important virulence factor produced by M. haemolytica on its leukocyte receptor bovine CD18. This finding lends itself to creating vaccines for shipping fever as well as cloning cattle that are resistant to M. haemolytica.

IP Status 

US and PCT applications pending    

Publication

Shanthalingam, Sudarvili and Srikumaran, Subramaniam. 2009. Intact signal peptide of CD18, the β-subunit of β₂-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin. PNAS 106 (36): 15448-15453

International Publication No. WO 2010/088691 A2

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.

IP Status

Patents issued in: US (6,073,072), Australia (763368) and several others pending.           

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives.

■  Provides a potentially cheaper method of production.            

IP Status

Patents issued in: US (7,153,676) and several others pending.  

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production. 

IP Status

US Patent No. 6,818,755 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives.

■  Provides a potentially cheaper method of production.           

IP Status

Patents issued in: US (6,287,835), Japan (3730918), Europe (00967189.2), Canada (2,387,971), and several others pending. 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.         

Applications and Advantages 

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production. 

IP Status

Patent pending in US.

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages 

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives.

■  Provides a potentially cheaper method of production.         

Abstract

WSU inventors have discovered transformed (transgenic) biocontrol agents for control of plant root diseases. In particular, the invention is directed to biologically pure cultures of transformed strains of fluorescent Pseudomonas species (spp.) which have a biosynthetic locus which encodes for the production of the antibiotic phenazine-1-carboxylic acid stably introduced into the genome, and which suppress (inhibit the incidence of or reduce the incidence or severity of) diseases caused by the soil-borne pathogen Rhizoctonia. Optionally, the strains suppress diseases caused by Pythium or diseases caused by Gaeumannomyces graminis (Gg) in addition to diseases caused by Rhizoctonia, or have the ability to control all three diseases.

Root diseases caused by Rhizoctonia, Pythium, and Gaeumannomyces graminis, cause a significant adverse impact on the production of important crops worldwide. The root disease take-all, caused by Gaeumannomyces graminis var. tritici (Ggt), Rhizoctonia root rot, caused by Rhizoctonia solani and R. oryzae, and Pythium root rot caused by any of several Pythium species, notably, Pythium ultimum and P. irregulare, are important root diseases of small grain crops, e.g., wheat, barley, triticale, and rye, worldwide.

Applications and Advantages

■   Offers a sustainable and environment-friendly alternative approach to control take-all and other soil-borne diseases.

IP Status 

US Patent (6,277,625; 6,447,770); Lithuania (4785); Australia (754319). Pending patent in Brazil, Canada, China, Europe, Israel, Japan,  Mexico, and South Korea

Abstract

These WSU technologies relate to reducing the incidence of C. jejuni bacteria infections in poultry and in humans, and more particularly to novel antigenic 5 compositions, vaccines, and methods for generating an immune response against C. jejuni bacteria in an animal.

Our research team has identified 30 “best-fit” antigenic composition or immunogenic membrane-associated C. jejuni proteins. These antigenic compositions are potentially valuable vaccine candidates that can be orally administered through the bird’s water or food supply. In research trials, these antigenic compositions have significantly reduced the pathogen's ability to colonize young chickens' intestines, where the infection begins. These technologies and methods could provide an effective alternative to antibiotics the poultry industry uses to control these pathogenic bacteria.

The methods developed for Campylobacter are, however, versatile enough to be used for (a) production of other vaccines; and (b) expressing difficult-to-express proteins because of cell toxicity type issues. In this latter case, the expression is facilitated because of the system’s ability to shunt proteins into the supernatant and not retain them within the cell.  This feature makes it easier also to purify the expressed protein.

Campylobacter jejuni is now the No. 1 food-borne pathogen in the United States and the world, surpassing Salmonella. In the United States alone, 2.4 million cases are reported annually, with with an estimated cost of treatment and loss of productivity of $8 billion annually. Humans are frequently infected with C. jejuni by handling or consuming raw poultry products. 

Applications and Advantages

Offers novel vaccine candidates and methods to generate immune response against Campylobacter jejuni in chickens, and other avian species.

IP Status 

US patent application pending

Abstract

The analysis of fatty acids has become increasingly important as more people are aware of their nutritional and health implications. As a result, a method for the analysis of fatty acids that provides both rapid and reliable results is of great value. Many methods are currently used to analyze fatty acids, however these methods are not convenient or direct and often must be optimized for specific reaction conditions. Researchers at Washington State University have developed a simple, robust, single-vial digestion and esterification procedure for the analysis of fatty acids in food products. Straightforward kits, containing the necessary reagents and procedures would be of great value to the market. The method employs commonly available chemicals, is not water sensitive and allows for the conversion of fatty acid salts, as well as the acyl components in all lipid classes such as triacylglycerols, phospholipids, sphingolipids, and waxes, to methyl esters using a simple direct single vial digestion & esterification procedure.

Applications and Advantages

■  Simple, non-moisture sensitive

■  Digestion and synthesis in a single vile

■  Does not require sample dehydration

IP Status 

US and PCT applications pending

Abstract

How carbon flux differentially occurs in vascular plants for protein synthesis, phenylpropanoid metabolism (i.e. lignins) and other metabolic processes is not well understood. Having previously discovered/validated that a six-membered arogenate dehydratase (ADT 1-6) family encodes the final step in Phe biosynthesis in Arabidopsis thaliana, this raised the fascinating question whether individual ADT isoforms (or combinations thereof) differentially modulated carbon flux to lignins, proteins, etc. WSU scientists obtained homozygous T-DNA insertion lines for 5 of the 6 ADTs, these being used to generate double/triple knockouts in all possible combinations. Various mutants gave phenotypes with profound but distinct reductions in lignin amounts and not accompanied by gross anatomical/growth and development defects, such as dwarfing. This is the first example of a plastid-localized metabolic step profoundly affecting carbon flux into lignin.

Applications and Advantages

This invention can facilitate further research, and development to further unravel the complexities of lignin biosynthesis at the cellular and tissue levels. Moreover, this offers opportunity to establish: specific roles of each ADT in various aspects of phenylpropanoid and lignin forming metabolic processes, including detailed metabolomic analyses, and a new means to probe lignin primary structure as well as the physiological consequences of lignin deposition reduction. Potential applications include controlling lignin flux where increased lignin can be exploited for production of commercially valuable compounds while decreased lignin can be exploited in the field of bioenergy.

IP Status

US provisional patent application pending

Publication

Man-Ho Cho, Oliver R. A. Corea, Hong Yang, Diana L. Bedgar, Dhrubojyoti D. Laskar, Aldwin M. Anterola, Frances Anne Moog-Anterola, Rebecca L. Hood, Susanne E. Kohalmi, Mark A. Bernards, ChulHee Kang, Laurence B. Davin, and Norman G. Lewis. Phenylalanine Biosynthesis in Arabidopsis thaliana. Identification and Characterization of Arogenate Dehydratases. The Journal of Biological Chemistry. 2007, 282 (42), 30827-30835

Abstract

WSU inventors have developed epoxy resin systems and carboxylic terminated polyesters using rosin acids as building blocks. This provides a method to make epoxy resin systems that do not contain Bisphenol A (BPA).

Current powder coating polyester resins are built largely on tere-or isophthalic acid and trimellitic anhydride as rigid monomers together with other reactants. The epoxy resin is either diglycidyl ethers of bisphenol A or epoxy-novolac resin, both are based on the phenol building block.

Rosin and derivative as adhesive tackifier is a well established practice, and they have also found many other niche applications in inks, varnishes, paints, sealing wax, adhesives, some soaps, dressing for machine belting; paper sizing; soldering, plasters, etc.

With an annual global growth of 7%, powder coating is the fastest growing business in coating industry. The global powder coatings market was $3.3 billions in 2002. The projected production will be 1,460,000 tons in 2006 and will increase to 2,295,000 by 2010. Among other advantages, the solvent-free process, ease of application, and few wastes are most impressive. Powder coatings include epoxy, polyester­epoxy, polyester, polyurethane, acrylic and others. Polyester epoxy hybrid coating takes almost half of total market. Powder coating is widely applied in automotive, furniture, wood, construction, appliance industries.

Applications and Advantages

• Environment-friendly procedure and non-hazardous product output to humans
• Wide application due to enhanced properties: great peeling properties and impact strength

IP Status 

US patent and PCT applications pending

Publication  

Honghua Wang, Bo Liu, Xiaoqing Liu, Jinwen Zhang and Ming Xian. Synthesis of Biobased Epoxy and Curing Agents using Rosin and the Study of Cure Reactions. Green Chem., 2008, 10, 1190-1196

Abstract

Data recently obtained at WSU indicates that a novel enzymatic methods can be used to significantly reduce the cost of Cr (III) analyses and of Cr(VI)/CR(III) speciation.  The method is based on the enzymatic transformation of nitrate to nitrite and observations that metals can selectively inhibit the rate of this transformation.  The activity if enzyme is determined via established techniques that provide a colorimetric determination of the rate of nitrite production. Using these methods, nitrite production, and this enzymatic activity can be determined quickly using a visible light spectrophotmeter or multi-well plate spectrophotometer.  Heavy metal toxicity can be identified by a decrease in the rate of nitrite production when compared to a control that has not been exposed tot eh heavy metal containing sample.  CR (III) inhibits the activity of nitrate reductase over a  concentration range of 1 to 10 mM.  An activity value of 100% indicates the rate of nitrate conversion in the absence of Cr(III). In very lean samples of CR(III), therefore, this technique could be used to directly measure the CR(III) concentration.

Often, however, it is of interest to measure Cr(III) concentrations in the presence of other metals (e.g. CD, Cu, Pb, Zn, and CR(VI)) at similar concentration.  As these metals can also inhibit the nitrate reductase activity such that specifically for Cr(III) analyses, the effects of these metals must be eliminated.  Through the  addition of 1mM nitrillotriacetetic acid (NTA), the inhibitory effects of these metals can be eliminated over typical concentrations of interest.  The addition of NTA removes the inhibitory effects of the other metal ions but does not affect the inhibitory capabilities of Cr(III)  Up to 10 mM NTA does not affect the inhibitory nature of CR(III) of the activity of nitrate reductase.

Further, with NTA eliminating the effects of many common metals, it is often desirable to measure Cr(III) concentrations in the presence of Cr(VI).  1 mM NTA does not eliminate the inhibitory effects of Cr(VI), and that to specifiate between Cr(III) and Cr(VI) further separation will be necessary.  In the hexavalent form, Cr(VI) usually occurs as chromate (CrO) and  dichromate (Cr2)7), with both of these species being divalent anions.  A separation can be effected by the addition of a small amount of anion exchange resin that  will scavenge the anionic Cr(VI) species leaving on the Ct(III) to inhibit the nitrate reductase activity.  This inhibition can be measured either in the lab or the field with a  multi-well plate spectrophotometer.  The multi-well plates could be pre-loaded with the proper amount of reagents including NTA and anion exchange resin to allow rapid analyses of many Cr(III) samples simultaneously (1-386).

Applications and Advantages

This is a novel analytical technique that has application in both the laboratory and in the field as a sensitive and cost effective technique for Cr(III) analyses, replacing the expensive ICP-MS measurements used for most routine applications.  Strong possibility likewise exists to substitute other enzymes for nitrate reductase.

IP Status 

US Patent 6,811,997; 7,169,290

Abstract

Bulk metallic glasses or bulk amorphous alloys (BAAs) have excellent glass forming ability and reduced glass transition temperatures leading to formation of amorphous structure at lower critical cooling rates of the order of 10³ K/s. In the recent years, multi-component Fe-based bulk amorphous alloys (BAAs) have attracted attention due their potential industrial applications in the areas where high wear and corrosion resistance are important. The excellent soft magnetic characteristics, high strength and good thermal stability of Fe-based amorphous alloy led to the development of new magnetic materials. However, downsides of this material, including limited amorphous phase-forming ability and high quenching rate, limited their structural processing in making bulk net shape BAA parts and wide industrial applications. 

WSU inventors were able to develop a process to demonstrate that net shape bulk amorphous components, for structural applications, can be fabricated using laser engineered net shaping (LENS ) by exploiting its current capabilities. LENS^TM  is an advanced rapid manufacturing technology offering the possibility of producing non-equilibrium microstructural features in metallic coatings and net shape components.

Applications and Advantages

■  LENS^TM  process can be used to investigate and fabricate structural parts using existing and new bulk amorphous alloys

■  SIGNIFICANT reduction of corrosion on treated metal surfaces.

This invention provides a novel amide bond formation strategy from simple thioacid and amine starting materials. The reaction is medicated by unstable but very reactive S-nitrosothioacid intermediates. This fast reaction under mild conditions should be used in synthesis.

Abstract

This WSU invention relates to a novel amide bond formation strategy from simple thioacids and amines. This process was mediated by reactive NTA (s-nitrosothioacids) intermediates. It revealed nitrosation as a novel strategy for thioacid activation. Compared to other amide formation methods, this reaction only utilized readily available organonitrite as the activation reagent. It took place under very mild reaction conditions, and the reaction rate was extremely fast. The chemistry is easily executed. It also showed excellent selectivity toward amines over hydroxyls.

Applications and Advantages

This synthetic method for peptide bond formation: 1) eliminates the need for protecting groups on oxygen bearing amino acid side chains and 2) facilitates peptide fragment coupling. The method also provides a high yield route for the chemical synthesis of proteins.

IP Status

US patent application

Publication

Pan, J, Devarie-Baez N, and Xian M. (2011). Facile amide formation via S-Nitrosothioacids. Org. Lett , 1092-1094.

Abstract

Hydrogen sulfide (H₂S) has been known as a toxic pollutant for years. However, H₂S, has been recently recognized as an important signaling molecule of the cardiovascular system, the inflammatory system and the nervous system. H₂S is now known as the third endogenous gaseotransmitter, alongside nitric oxide (NO) and carbon monoxide. There is rising interest on H₂S research; however, questions still remain on how to regulate H₂S production, its mechanism of action, and destruction. Understanding these processes and the function of H₂S require accurate and reliable measurement of H₂S concentrations, which at present cannot be provided by available methods such as colorimetric and electrochemical assays, gas chromatography, and sulfide precipitation.

WSU inventors have developed a reaction-based fluorescent turn-on strategy for the detection of H₂S. This strategy involves a proprietary process and a reagent that selectively reacts with H₂S to yield a fluorescent reporter. The fluorescense response is linear with H₂S concentration.

Applications and Advantages

■ Offers simple sample processing

■ High sensitivity

IP Status

Available for non-exclusive licensing

Abstract

Hydrogen sulfide has demonstrated several essential critical care benefits when delivered properly in low doses. The current state of the art delivery systems rely on gaseous delivery of H₂S to patients. We are developing chemical agents that controllably decompose to release H2S. 

Applications and Advantages

■   Timed release 

■   Biocompatable

IP Status 

US patent application(s) pending

Abstract

Currently in development at WSU is a methodology to make super-toughened polylactic acid (PLA) blends in which PLA content is more than 80 wt%. The resulting blends display not only super toughness (impact strength >800 J/m) but also high ductility (tensile elongation > 200%) and moderate tensile strength.

Applications and Advantages

■   Bio-degradable

■   Good impact toughness

■   Meltprocessability

IP Status 

US patent application(s) pending

Abstract

This WSU invention relates to mesoporous calcium silicate compositions and methods for producing mesoporous calcium silicate for controlled release of bioactive agents (i.e. proteins, growth factors, pharmaceutical drugs, antibiotics, polypeptides, etc.).  Using hydrochloric acid at different pH, mesoporous calcium silicate was synthesized by acid modification of wollastonite. A hydrated silica gel with abundant Si-OH functional group was formed on the surface. Bruhauer-Emmettt-Teller (BET) surface area increased significantly due to acid modification and reached over 350 m²/g. Acid modified mesoporous calcium silicate particles demonstrate an increased ability to adsorb protein compared to unmodified calcium silicate particles, and further demonstrate controlled release kinetics of these proteins.

Applications and Advantages

■  Offers calcium silicate materials for use in bone implant applications with increased bioactivity and bioactive agent loading.

IP Status 

US patent application pending

Abstract

During the torrefaction and pyrolysis of lignocellulosic materials, a sizable fraction of the biomass (8 - 15 mass %) is converted into C2 - C4 oxygenated organic compounds. These small organic compounds can be condensed and recovered in the form of an aqueous phase containing up to 50 mass % of these organic compounds. Formic acid, acetic acid, propionic acid, methanol, glycoaldehyde, and acetol are the main small molecules produced by pyrolysis and torrefaction. During the 19th and 20th centuries, most of the methanol (wood alcohol), acetic acid and acetone consumed in the world was produced by refining aqueous phases produced by the slow pyrolysis of wood (wood distillation). With the creation and expansion of the petroleum industry in the first half of the 20th century and with the development of cheaper catalytic routes to produce methanol, the interest in producing and utilizing C1 - C4 oxygenated compounds via biomass pyrolysis disappeared. In fact the production of these small molecules is currently considered a serious environmental problem limiting the deployment of pyrolysis and torrefaction units for bio-fuel and bio-power production.

Applications and Advantages

Anaerobic digestion offers an excellent opportunity to convert these small molecules with limited market into methane which is a very good energy carrier for hydrogen production in rural bio-oil refineries. Furthermore, co-digesting C1 - C4 oxygenated molecules from torrefaction and pyrolysis units in anaerobic digesters at dairy farms will spur rural economic development by helping our farmers to increase their profits.

IP Status

US patent application

Abstract

WSU inventors have developed epoxy resin systems and carboxylic terminated polyesters using rosin acids as building blocks. This provides a method to make epoxy resin systems that do not contain Bisphenol A (BPA).

Current powder coating polyester resins are built largely on tere-or isophthalic acid and trimellitic anhydride as rigid monomers together with other reactants. The epoxy resin is either diglycidyl ethers of bisphenol A or epoxy-novolac resin, both are based on the phenol building block.

Rosin and derivative as adhesive tackifier is a well established practice, and they have also found many other niche applications in inks, varnishes, paints, sealing wax, adhesives, some soaps, dressing for machine belting; paper sizing; soldering, plasters, etc.

With an annual global growth of 7%, powder coating is the fastest growing business in coating industry. The global powder coatings market was $3.3 billions in 2002. The projected production will be 1,460,000 tons in 2006 and will increase to 2,295,000 by 2010. Among other advantages, the solvent-free process, ease of application, and few wastes are most impressive. Powder coatings include epoxy, polyester­epoxy, polyester, polyurethane, acrylic and others. Polyester epoxy hybrid coating takes almost half of total market. Powder coating is widely applied in automotive, furniture, wood, construction, appliance industries.

Applications and Advantages

• Environment-friendly procedure and non-hazardous product output to humans
• Wide application due to enhanced properties: great peeling properties and impact strength

IP Status 

US patent and PCT applications pending

Publication  

Honghua Wang, Bo Liu, Xiaoqing Liu, Jinwen Zhang and Ming Xian. Synthesis of Biobased Epoxy and Curing Agents using Rosin and the Study of Cure Reactions. Green Chem., 2008, 10, 1190-1196

Abstract

Improvements in plant productivity (biomass) and yield have centered on increasing the efficiency of leaf carbon dioxide fixation and utilization by non-photosynthetic sink organs. This technology focuses on exploiting leaf starch synthesis as a transient sink to increase plant productivity and yields. In particular, transgenic Arabidopsis were used as examples where mutant transgenic plants were shown to exhibit enhanced photosynthetic capacity that translated into increased growth and biomass.  

Applications and Advantages

• Offers a viable alternative strategy to increase productivity and yields of crop and bio-energy plants.

IP Status

US provisional patent

Abstract

Wood-plastic composite is a very promising and sustainable green material that is produced for its ability to be durable without containing toxic chemicals. WSU has patented an invention that relates to the low-cost and efficient procedure of making low density cellular wood plastic composite with wood flour and high-density polyethylene wherein the ratio of wood flour to high-density polyethylene ranges from 1:4 to 3:2.  The following three steps outline this process of producing cellular wood plastic composite:

1)   mixing finely ground wood flour with plastic in an extruder to form a plasticated mixture;

2)   introducing a blowing agent into the plasticated material under pressure sufficient to drive the blowing agent into the plasticated mixture to form cells within the plasticated mixture, wherein the blowing agent is introduced under a pressure gradient in the extruder sufficient to increase the solubility of the blowing agent in the plasticated mixture and under a temperature sufficient to prevent collapse of the cells; and

3)    reducing the pressure prior to removing the plasticated mixture from the extruder.

Applications and Advantages

■  stable and low density;

■  use of low-cost materials for production (i.e. blowing agent);

■  better product output: increased stiffness

IP Status 

US Patent 7,431,872; Australia 2002259018; New Zealand 529062. Several others pending in Canada, Europe, Japan, and Mexico

Abstract

This technology involves the production of chavicol/eugenol and potential and current applications in antibacterials/plant defense/analgesics, polymer building blocks, and in biofuel/bioenergy production.

One of the major potential sources of renewable energy/biofuels being considered is that from plant biomass, i.e. through fermentation of polymeric carbohydrates to give ethanol.  There are two major scientific hurdles that have not yet been overcome in this process.  The first is that of the polymeric lignins, which make up ca. 20-30% of all plant stem biomass, and which are nature’s second most abundant organic materials. Under current fermentation processes, lignins cannot readily be converted into either ethanol and/or other liquid/gaseous fuels.  Indeed, there are still no isolated enzymes and/or proteins known to effectively degrade the lignin macromolecules. Secondly, the polymeric lignins themselves represent a formidable physical barrier in biomass for efficient carbohydrate fermentation. Thus, their presence represents a critical barrier in making these technologies more economical.  WSU’s proposed solution to these is diverting monolignol flow away from lignin biopolymer formation, or from heartwood lignan accumulation/deposition, to that engendering formation of the potential product liquid fuels/intermediate chemicals of interest i.e., eugenol and chavicol. This WSU technology, hence, focuses in the:

■ production of chavicol/eugenol in bacterial and plant cell cultures;

■ transformation of either oilseed (e.g., rapeseed) or heartwood-forming plants to produce, in large quantity, chavicol and eugenol;

■  production of the biopolymers or intermediates for the chemical industry; and

■  making cellulosic ethanol production more efficient by virtue of less lignin and easier fermentation                       

Applications and Advantages

■        offers methods for redirecting carbon allocation in plants or cell culture from lignification to more useful and tractable materials, and to facilitate the generation of, e.g. biofuels from the remaining plant to culture biomass; and

■     provides a novel way to more effectively utilize the lignin biopolymers and/or the carbon allocated for the lignin-forming pathway.

IP Status

US, and Europe patent applications pending

Publication

US patent publication no. US20100031398 A1

Europe patent publication no. EP 2046110

Vassão, DG, Kim SJ, Milhollan JK, Eichinger D, Davin LB and Lewis NG. (2007).  A pinoresinol-lariciresinol reductase homologue from the Creosote bush (Larrea tridentata) catalyzes the efficient in vitro conversion of p-coumaryl/coniferyl alcohol esters into the allylphenols chavicol/eugenol, but not the propenylphenols p-anol/isoeugenol. Archives of Biochemistry and Biophysics 465. 209–218

Abstract

The invention is a new wheat genotype, with tolerance to glyphosate herbicide at practical application levels. This genotype was developed via traditional mutation breeding and selection and did not involve transgenic approaches.

Weed control is the primary yield limiting factor in wheat production, which impacts essentially every acre in commercial production worldwide.  Cost effective, efficient, environmentally friendly weed control methods are essential to sustainable wheat production.  This discovery offers the possibility of creating non-transgenic, glyphosate tolerant wheat cultivars.  Gene(s) associated with glyphosate tolerance identified through this research could be introgressed into adapted germplasm from every wheat producing region in the world through conventional breeding, eliminating market acceptance and perception issues against transgenic crops.

Applications and Advantages

■  Non-transgenic technology that offers growers/farmers reduce mechanical weed control by selectively and effectively controlling glyphosate sensitive weeds after crop emergence;

■  Offers improved weed control that may eventually lead to no-till wheat production, resulting to enhanced profitability and likewise promoting for economic and environmental sustainability in wheat farms. 

IP Status

US and PCT applications pending    

Publication

PCT publication WO 2007092505 A2

Abstract

Pretreatment of lignocellulosic biomass to separate lignin and cellulose and hemicelluloses is a necessary step before ethanol fermentation by yeast. Furfural, a key inhibitor of yeast, is produced during heating in the pretreatment. Several approaches have been tried to deal with furfural toxicity in lignocellulosic hydrolysate but all have limitations.

WSU inventors found a new and faster method to reduce furfural by Ralstonia eutropha JMP134 at a wide range of ionic strengths, pH, and temperature. JMP134 was found to reduce furfural with maximal rates of 2.4 and 7.2 μmol min-¹ at 24C and 50C, respectively, 12 and 36 times faster than the maximal report rate for yeast. Reduction of furfural will shorten the lag phase and fermentation time, hence, high outputs of ethanol, and increased productivity in commercial ethanol production. 

Applications and Advantages

■  Offers a new and more environment-friendly approach to increase productivity in ethanol production

IP Status 

US patent application pending

Abstract

Currently in development at WSU is a methodology to make super-toughened polylactic acid (PLA) blends in which PLA content is more than 80 wt%. The resulting blends display not only super toughness (impact strength >800 J/m) but also high ductility (tensile elongation > 200%) and moderate tensile strength.

Applications and Advantages

■   Bio-degradable

■   Good impact toughness

■   Meltprocessability

IP Status 

US patent application(s) pending

Abstract

Phosphorus (P) could be recovered from animal wastewater in the form of struvite (ammonium magnesium phosphate) to be used as a slow-release fertilizer; however, the majority of P in anaerobically digested dairy effluent is tied up in a fine suspended calcium-phosphate solid, thus becoming unavailable. P liberation through acidification and sequestering calcium with citric acid and a chelating agent was investigated. The acidification results demonstrated that most of the P in the digested dairy effluent was released into solution by pH depression.  The citric acid, on the other hand, sequestered calcium through strong bonding of citrate with calcium. The P concentration in solution increased significantly with increased citric acid, confirming that most of the P can be liberated from its suspended solid.  Similar results were obtained from the use of a chelating agent, ethylenediaminetetraacetic acid (EDTA), which has a high stability constant, with calcium as an EDTA-calcium complex dissolved in solution.  In addition, the freed P was shown to be precipitated as struvite be ensuring sufficient Mg2+ ions present in solution.  Furthermore, the solid precipitate obtained from the EDTA treatment was investigated using X-ray diffraction (XRD) analysis, verifying that the phase structure of the precipitate matched well with standard struvite. Our results not only further confirmed the existence of P in an inorganic particulate formed in anaerobically digested dairy effluent, but also provided methods to release P to make it available for struvite production.  In addition, the results have practical implications in the design and application of P removal technologies for dairy wastewater management.

Applications and Advantages

■  Provides means for applying a single product as effective fungicide and effective fertilizer

■  Formulation is very storage stable

IP Status

US patent application pending

Abstract

Camelina is one of the crops that is being actively explored and researched in recent days for its potential use as a biofuel crop. Value-added traits that would reduce input costs should aid in exploiting this crop as an alternative fuel crop. This particular technology relates to the use of Arabidopsis/Camelina derived AHL genes and gene products for modulation of cell growth in plants. Our WSU investigators have discovered that mutations within the A-T hook domain confer a dominant negative phenotype to the plants resulting in longer hypocotyls and taller seedlings. 

The practical utility of this discovery is that Camelina can be planted deeper enabling the growing seed to tap into deeper water sources.  This should make it particularly attractive and useful in dryland agriculture. In addition to its utility in Camelina, the mutants can be exploited in other crops of commercial value.

Applications and Advantages

Offers to transform the oilseed, camelina as a better biofuel crop using transgenic technology

IP Status 

US patent application pending

Publication 

Street IH, Shah PK, Smith AM, Avery N, and Neff MM (2008). The AT-hook containing proteins SOB3/AHL29 and ESC/AHL27 are negative modulators of hypocotyl growth in Arabidopsis. Plant Journal 54. 1-14.

Abstract

During the torrefaction and pyrolysis of lignocellulosic materials, a sizable fraction of the biomass (8 - 15 mass %) is converted into C2 - C4 oxygenated organic compounds. These small organic compounds can be condensed and recovered in the form of an aqueous phase containing up to 50 mass % of these organic compounds. Formic acid, acetic acid, propionic acid, methanol, glycoaldehyde, and acetol are the main small molecules produced by pyrolysis and torrefaction. During the 19th and 20th centuries, most of the methanol (wood alcohol), acetic acid and acetone consumed in the world was produced by refining aqueous phases produced by the slow pyrolysis of wood (wood distillation). With the creation and expansion of the petroleum industry in the first half of the 20th century and with the development of cheaper catalytic routes to produce methanol, the interest in producing and utilizing C1 - C4 oxygenated compounds via biomass pyrolysis disappeared. In fact the production of these small molecules is currently considered a serious environmental problem limiting the deployment of pyrolysis and torrefaction units for bio-fuel and bio-power production.

Applications and Advantages

Anaerobic digestion offers an excellent opportunity to convert these small molecules with limited market into methane which is a very good energy carrier for hydrogen production in rural bio-oil refineries. Furthermore, co-digesting C1 - C4 oxygenated molecules from torrefaction and pyrolysis units in anaerobic digesters at dairy farms will spur rural economic development by helping our farmers to increase their profits.

IP Status

US patent application

Abstract

WSU inventors have discovered transformed (transgenic) biocontrol agents for control of plant root diseases. In particular, the invention is directed to biologically pure cultures of transformed strains of fluorescent Pseudomonas species (spp.) which have a biosynthetic locus which encodes for the production of the antibiotic phenazine-1-carboxylic acid stably introduced into the genome, and which suppress (inhibit the incidence of or reduce the incidence or severity of) diseases caused by the soil-borne pathogen Rhizoctonia. Optionally, the strains suppress diseases caused by Pythium or diseases caused by Gaeumannomyces graminis (Gg) in addition to diseases caused by Rhizoctonia, or have the ability to control all three diseases.

Root diseases caused by Rhizoctonia, Pythium, and Gaeumannomyces graminis, cause a significant adverse impact on the production of important crops worldwide. The root disease take-all, caused by Gaeumannomyces graminis var. tritici (Ggt), Rhizoctonia root rot, caused by Rhizoctonia solani and R. oryzae, and Pythium root rot caused by any of several Pythium species, notably, Pythium ultimum and P. irregulare, are important root diseases of small grain crops, e.g., wheat, barley, triticale, and rye, worldwide.

Applications and Advantages

■   Offers a sustainable and environment-friendly alternative approach to control take-all and other soil-borne diseases.

IP Status 

US Patent (6,277,625; 6,447,770); Lithuania (4785); Australia (754319). Pending patent in Brazil, Canada, China, Europe, Israel, Japan,  Mexico, and South Korea

Abstract

WSU researchers have developed a novel design which improves the performance of piezoelectric transducers. Laminated piezoelectric transducers are useful for acoustic transduction, fluid pumping, and power generation, among many applications.

The newly developed transducer design can induce large increases (at least 4X) in the displacement amplitude of a piezoelectric diaphragm per unit supplied voltage. This phenomenon directly increases the acoustic pressure (the loudness) produced by a piezoelectric diaphragm when used as a sound source. Reversely, this effect translates into high sensitivity of the diaphragm when used as a receiving transducer, or microphone. This is also useful across a wide range of frequencies for emergency audio tones, status alerts (like for phones), and variable (potential for speaker-like audio quality).

This novel approach can significantly increase the sensitivity of a piezoelectric diaphragm when used as an electro-acoustic transducer. Power consumption for such a transducer is potentially much lower than competing electromagnetic technology, with no electric coil to dissipate energy. Electromagnetic speakers are currently used in small-scale devices, such as cellular telephones. Use of power-saving speaker technology in applications like cell phones has potential to increase battery life.

Future Applications

■  Cell phones

■  PC & small electronics speakers, microphones

■  Medical ultrasound devices

■  Sonar devices

IP Status 

US Patent No. 7,710,001

Abstract

WSU researchers have created a novel architecture for improving the performance of a router. Using interleaved multistage switching fabrics, this architecture creates a faster router which is scalable and has greater fault tolerance. This technology is applicable to delta-class networks such as: baseline, reverse baseline, Omega, Banyan, and N-cube.

Routers can be evaluated on the basis of scalability, reliability, and cost. In this design, a self-routing method was used to solve for high routing complexity, making it scalable for next generation networks. This invention provides higher performance and reliability than normal delta class self-routing multistage interconnection networks.

Applications and Advantages

■  Faster – speedups (over single panel fabric) of 3.4 and 2.25 under uniform and hot-spot traffic patterns at maximum load

■  Scalable – for next generation networks

■  Improved fault tolerance – better performance and reliability than normal delta class self-routing multistage interconnection networks

IP Status 

US patent applications pending

Abstract
This WSU invention addresses a pressing need in the analysis of large number of force-distance curves generated in force microscopy techniques such as atomic force microscopy (AFM) and applying different models to characterize a variety of synthetic and biological materials. This efficient algorithm and program can analyze and model several thousand force-distance curves within minutes. Current version of the program overcomes many difficulties and uncertainties that are associated with analysis of force-distance curves and applies Hertz, cubic, and steric models. The program yields parameters such as stiffness, Young's modulus, force of adhesion, dilation modulus, density of molecules, and material thickness in molecular dimension. The program has been applied to the analysis of over 15,000 force-distance curves generated for prostate cancer cells from benign to highly metastatic in character. Results indicate differences in the various parameters of the cells characteristic of their nature.

Applications and Advantages

The algorithm and program enables the characterization of complex materials such as biological materials by force microscopy that could provide new insights into phenomena associated with them. It can be a valuable tool for both fundamental investigations and practical applications.

IP Status

Available for Licensing

Abstract

Personnel rostering in operational settings -- e.g., air, road, rail and sea transportation, first responders (police, fire, and rescue), medicine, power generation, resource extraction, and military operations – has, thus, far centered on the logistics of resources and availability of employees, largely ignoring the performance capability of the employees as driven by their sleep/wake biology.  Thus, rosters involving shift work and periods of extended wakefulness often cause individuals to work at times of increased sleepiness and reduced alertness and performance due to sleep loss and unfavorable timing on the endogenous biological clock; and conversely to attempt sleep when sleep is compromised by pressure for wakefulness from the endogenous biological clock.  This puts organizations and individuals at risk for poor performance, increased errors, diminished productivity, accidents, and reduced safety.

Recent developments in biomathematical modeling of performance on the basis of sleep/wakefulness have made it possible to predict times of increased sleepiness in groups of workers. This has made it feasible to optimize sleep/wake/work schedules not only on the basis of resource logistics, but also on the basis of sleep/wake-based performance prediction.

WSU inventors have developed a system and procedure for rostering and scheduling to reduce fatigue and its consequences by integrating mathematical models capable of predicting fatigue with software/hardware components capable of optimizing rosters and/or work schedules. As a result, rosters/schedules that are conducive to good performance while meeting operational demands for personnel and complying with applicable regulations can be produced. The resulting rosters and/or work schedules can help to sustain performance, productivity, safety, and well-being, while reducing errors, incidents, accidents, and attendant human and economic losses.

Applications and Advantages

■   Provides a modern approach for rostering and optimizing work schedules;  

■   Offers a fatigue model that is adjustable to predict objectively measurable loss in productivity (e.g., in transportation--increased fuel consumption and increased maintenance) and other operationally relevant performance outcomes.

IP Status 

US patent and PCT applications pending

Abstract

This WSU invention relates to a low-cost smart parking guidance system which combines monitoring, communication, processing and variable-message sign technologies to provide the service. The method is based on wireless sensor networking technology and provides the guidance on:

■   whether a parking lot has free spaces

■   how to get to the nearest free space in shortest path

Aside from being cost-effective, this technology can be customized according different level of parking guidance needs. The parking guidance is calculated by the self-organizing and self-healing network itself and does not depend on any central stations. It provides real-time and fault-tolerant parking guidance, and can be easily applied to emergency escape guidance scenario. With the novelty of the proposed algorithm, it can be extended to various customized parking guidance needs. The social impact of the proposed system is as significant as the technology innovations. It can help to reduce the time spent searching for a parking space, the energy cost and pollutant emissions due to reduction in overall travel time, the accidents due to happier drivers, among others. The adoption of a smart guidance system can also raise the public image of the area, which in turn can lead to improved revenue generation within that area.

Abstract

The Speakeasy Studio & Cafe is a web-conferencing software that enables people to communicate with one another in real-time (chatroom) or "asynchronously" (in threaded-discussion forums).  It is a platform upon which the framework for a digital online classroom complete with tables, chairs, assignments, blackboards, and interactive discussions between students and teacher can be built.

Applications and Advantages

■   organizes conversations and security accesses, allowing for terrific ease of scalability;

■   can be accessed from any internet terminal and computers running a variety of different operating systems.

IP Status 

Copyright registered.

Abstract

The availability of small, low-power devices, which filter, amplify and transmit weak electrophysiological signals, has traditionally been a bottleneck in the development of subject monitoring equipment. Current state of the art equipment utilizes relatively few electrodes operating over a relatively narrow frequency range at relatively low speed. Due in part to the limited availability of high performance devices, data outside the frequency and intensity regime provided by current instrumentation has been sparse. This has led to a false impression that data outside of the parameters is of little importance, which in turn has led to a slow to develop demand for such high performance devices.

Recent studies exploiting custom built high performance instrumentation have demonstrated the need for such high performance devices. While this is becoming apparent to those within the industry, there is presently a race to develop devices with increased capabilities. At present, a WSU team has a device that vastly out-performs the current state of the art.

WSU researchers have developed a small, highly sensitive, low-cost system capable of processing, correlating and wirelessly transmitting data from events occurring at frequencies ranging from DC to 7kHz. The signal processing component is contained on a single chip, which can independently process 16 channels of information. Moreover, custom designed software and hardware with the capability to control individual channels in real time, correlate the signals in time to a video feed and communicate with multiple signal processing chips. The current prototype of the device is operable for the measurement of EEG (electroencephalography) in laboratory mice. System attributes include: DC coupled, high sensitivity (1mv), 110 dB dynamic range, 24 bit ADC sampling 16-256 channels @ 32kHz and optimized for minimal power consumption.

Applications and Advantages

■  Lightweight

■  Wide frequency range

■  DC coupled- allows for errors in positioning and enables processing of DC signals

■  High sensitivity and dynamic range

IP Status 

US and PCT applications pending

Abstract

WSU staff have developed a simple, easy to use suite of applications for web publishing. While there are many content management systems currently on the market, none fill the specific set of criteria important for large organizations wherein many users are able to edit and modify information published on the web. Specifically, Universities, School Districts and some large companies have many individuals editing the content on their web pages; a perennial challenge in such settings is: How does the organization retain the branding elements necessary to coherently represent the organization? WSU has developed a Content management system and suite of plug-in tools that enable users to modify content on their organizations web site without modifying the stylistic elements of the site.

Applications and Advantages

■  Web-based: does not require installation of software

■  Easy to use: requires only a basic knowledge of word processing programs to operate

■  Versatile: many plug in applications available

Abstract

WSU researchers have developed piezoelectric energy harvesting devices for applications aimed to convert human motion, low-frequency vibrations and acoustic noise into electrical energy. This technology uses a resonating mass-spring device to convert some of the mechanical energy imparted to it from an external vibrating energy source to electrical energy, which is useful for low-power sensing and information transmission applications. Ambient vibrations exist at frequencies in the 10’s to 100’s of Hz. Power harvesting is optimized at resonant frequencies of the device. The resonant frequency can be varied over a wide range – achieving flexible and complete frequency tunability.

Future Applications

The ability to power sensor nodes and transmission systems requires a non-battery solution. Vibration harvesting is critical to military and civilian infrastructure operations.

IP Status 

US patent application pending

Abstract

A course evaluation form for traditional classrooms use composed of 36 question that address seven major factors: 1) instructor communication; 2) instructional resources; 3) responsiveness to students; 4) learning outcomes; 5) student responsibility and examinations; 6) work load; and 7) student effort. The validity of this form was tested against commercially available forms (Kansas State's IDEA system) during Spring semester 1996 in 5 WSU psychology courses (N=399) and 25 Psychology courses (N-574), this form is now being used by many WSU departments.   

IP Status 

Copyright registered.

Abstract

DC to DC switching power supplies operate by storing energy in inductors, capacitors, or both, then distributing this energy to a load over a time period.  An efficient method used to accomplish this task is to vary the charging time for the energy storage devices depending on the load, for every time period.  This is known as pulse width modulation (PWM) where the charging time per period changes with respect to the load.  Another method is to use pulse code modulation (PCM) where the average value of the control signal keeps the output voltage near the desired level. This invention presents a new digitally programmable structure for the control of DC to DC switching power supplies.  These controllers are stable under DC and low frequency load changes.  The PCM controller eliminates the requirement of existing PWM controllers for matching between the current source and capacitor in the ramp generator.  Both controllers are insensitive to offsets that may exist in design.

Applications and Advantages

■  Provides an improved DC-to-DC switching power supply converter design which provides for the precise, low drift control of output voltage with high efficiency and simplicity of design.

IP Status 

US Patent No. 5,677,618

Abstract

WSU researchers have developed a novel design which improves the performance of piezoelectric transducers. Laminated piezoelectric transducers are useful for acoustic transduction, fluid pumping, and power generation, among many applications.

The newly developed transducer design can induce large increases (at least 4X) in the displacement amplitude of a piezoelectric diaphragm per unit supplied voltage. This phenomenon directly increases the acoustic pressure (the loudness) produced by a piezoelectric diaphragm when used as a sound source. Reversely, this effect translates into high sensitivity of the diaphragm when used as a receiving transducer, or microphone. This is also useful across a wide range of frequencies for emergency audio tones, status alerts (like for phones), and variable (potential for speaker-like audio quality).

This novel approach can significantly increase the sensitivity of a piezoelectric diaphragm when used as an electro-acoustic transducer. Power consumption for such a transducer is potentially much lower than competing electromagnetic technology, with no electric coil to dissipate energy. Electromagnetic speakers are currently used in small-scale devices, such as cellular telephones. Use of power-saving speaker technology in applications like cell phones has potential to increase battery life.

Future Applications

■  Cell phones

■  PC & small electronics speakers, microphones

■  Medical ultrasound devices

■  Sonar devices

IP Status 

US Patent No. 7,710,001

Abstract

WSU researchers have developed piezoelectric energy harvesting devices for applications aimed to convert human motion, low-frequency vibrations and acoustic noise into electrical energy. This technology uses a resonating mass-spring device to convert some of the mechanical energy imparted to it from an external vibrating energy source to electrical energy, which is useful for low-power sensing and information transmission applications. Ambient vibrations exist at frequencies in the 10’s to 100’s of Hz. Power harvesting is optimized at resonant frequencies of the device. The resonant frequency can be varied over a wide range – achieving flexible and complete frequency tunability.

Future Applications

The ability to power sensor nodes and transmission systems requires a non-battery solution. Vibration harvesting is critical to military and civilian infrastructure operations.

IP Status 

US patent application pending

Abstract

Piezoelectric oxide films, such as lead zirconte titanate (PZT), are now being integrated into micro-electro-mechanical systems (MEMS) applications.  Many PZT derived systems are deposited using a sol-gel process, which can be used in a microelectronics processing route using spin coating as the deposition method. An application of interest for PZT films is in power generation, where a flexing membrane is used to transform mechanical to electrical energy.  This research was undertaken at WSU to identify the relationships between the processing, microstructure, and mechanical reliability of these films. Films were deposited onto both monolithic and bulk micromachined platinized silicon wafers using standard sol-gel chemistries, with roughness and grain sie tracked using electron and scanning probe microscopy.  Mechanical properties were evaluated in a dynamic bulge testing apparatus. Grain size variations in the Pt film between 35 and 125 nm are shown to have little effect on grain size of the subsequent PZT film and the adhesion of the PZT to the Pt film.  Only the Pt film with 125 nm grains was shown to undergo any significant interfacial fracture.  Fatigue tests suggest film lifetime is primarily limited by the number of pre-existing flaws in the film from processing. Reducing the microcrack density has been shown to produce films and devices that fail at strains of 1.4% and have mechanical fatigue lifetimes in excess of 100 million cycles at strains simulating the operating conditions.

Applications and Advantages

■   Offers a thermal switch that enables the precise control of heat transfer into and out of MEMS devices.

IP Status 

Patent pending in US, Australia, Canada, and Europe

Abstract

WSU researchers have developed piezoelectric energy harvesting devices for applications aimed to convert human motion, low-frequency vibrations and acoustic noise into electrical energy. This technology uses a resonating mass-spring device to convert some of the mechanical energy imparted to it from an external vibrating energy source to electrical energy, which is useful for low-power sensing and information transmission applications. Ambient vibrations exist at frequencies in the 10’s to 100’s of Hz. Power harvesting is optimized at resonant frequencies of the device. The resonant frequency can be varied over a wide range – achieving flexible and complete frequency tunability.

Future Applications

The ability to power sensor nodes and transmission systems requires a non-battery solution. Vibration harvesting is critical to military and civilian infrastructure operations.

IP Status 

US patent application pending

Abstract

WSU inventors have developed a prototype trap that can store significant quantities of positrons that can create a tremendous amount of energy. Particles of antimatter, positrons, probes the basic interactions and properties of matter and has broad potential applications, including development of a new and high quality computer microchips, detecting atomic size defects in thin layers or surfaces of materials, etc.

Applications and Advantages

■   Provides a stable method to store positrons hence prevent premature annihilation.

IP Status 

US patent application(s) pending

Abstract

Pretreatment of lignocellulosic biomass to separate lignin and cellulose and hemicelluloses is a necessary step before ethanol fermentation by yeast. Furfural, a key inhibitor of yeast, is produced during heating in the pretreatment. Several approaches have been tried to deal with furfural toxicity in lignocellulosic hydrolysate but all have limitations.

WSU inventors found a new and faster method to reduce furfural by Ralstonia eutropha JMP134 at a wide range of ionic strengths, pH, and temperature. JMP134 was found to reduce furfural with maximal rates of 2.4 and 7.2 μmol min-¹ at 24C and 50C, respectively, 12 and 36 times faster than the maximal report rate for yeast. Reduction of furfural will shorten the lag phase and fermentation time, hence, high outputs of ethanol, and increased productivity in commercial ethanol production. 

Applications and Advantages

■  Offers a new and more environment-friendly approach to increase productivity in ethanol production

IP Status 

US patent application pending

Abstract

New food products, particularly those that both improve nutrition or decrease immunological response in comparison to their gluten-containing counterparts, are always desirable. Most importantly, new foods that taste good are always appreciated by consumers, particularly if they can be stored easily and allow flexibility in recipes. WSU food scientists have developed a suite of novel dairy products that can serve as substitutes for a number of common foods. For example, these products offer gluten free, low carb alternatives for many wheat-based food products or as meatless patties in a burger. The processing is similar to traditional cheese making and allows for a range of modifications to enable the tailoring of fat content or integration with seasonings and vegetable matter.  

Applications and Advantages

■   Provides a technology platform for a line of dairy based products for different market segments

IP Status 

PCT application pending

Abstract

This all-natural, ready-to-bake chocolate cake sports an erupting volcano (with flavored lava), island-theme decorations, and gummy dinosaurs. The target audience for Erupt-a-Cake is ‘tweens’ aged 8 – 12 years old.

This new product will not only excite children’s eyes and provide unforgettable party experiences, but will stimulate their interest in science by teaching basic food science principles. The kids make the cake and learn some science by combining an acid and a base to create the reaction that makes the volcano erupt. This product comes in a kit with components to assemble Erupt-a-Cake and educational material explaining the science behind the reaction in one convenient package.

Applications and Advantages

■   Uses natural ingredients hence safe for children to work with and eat;

■   Provides consumers with a “home-made” appeal;

IP Status 

Product know how and compositions are available for exclusive worldwide licensing.

Abstract

Grain or legume material is pre-cooked by a low moisture process and pre-conditioned by hydrating to a total moisture content of from about 10% to about 40% by weight, passed through a cooking extruder and, during such passage, hydrated to a total moisture content of from about 10% to 40% by weight, extruded and dried.  The products of the invention are crisp curls, puffs, and chips.  The extruded cooked material may also be ground and agglomerated to prepare powders which will not cake or lump.

Applications and Advantages

The uniform expansion ratio possessed by the extruded product provides a consistent texture and has application in a wide variety of food consumables, from snacks to breakfast cereals.

IP Status

US patent and PCT applications pending

Publications

US Patent Publication No. 2008-0145483 A1

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.       

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.    

IP Status

Patents issued in: US (7,402,417); and several others pending. 

Abstract

Vaccination of pigs against porcine reproductive and respiratory syndrome virus (PRRSV) is the most prudent and logical way of controlling this economically important disease which costs over $600 million annually to the US pork industry. Production of vaccines requires large scale propagation of PRRSV in the laboratories of pharmaceutical companies.  The cell-line that is currently available for propagation of PRRSV in vitro is the green monkey kidney epithelial cell-line (and its derivatives), which has been patented by Boehringer Ingelheim.  Availability of additional cell-lines for propagation of PRRSV should enhance the development of vaccines by several Biologics Companies, which will increase the likelihood of several efficacious vaccines against PRRSV becoming available in the future.

WSU inventors employed transfection techniques to develop macrophage cell-lines suitable for propagation of PRRSV in vitro.  Sialoadhesin has been identified as the receptor for PRRSV om PAMs.  Transfection of porcine sialoadhesin into macrophage cell-lines from other species should render them peremissive for PRRSV replication.  The gene encoding porcine sialoadhesin were then cloned, sequenced, and the transfected it into a mouse macrophage cell-line (J774A.1).  One transfectant was subjected for further studies and found to be permissive for PRRSV replication. PRRSV replicates to a titer of 1x105. 

This WSU transfectant macrophage cell line could then be used for propagation of PRRSV for the development of vaccines against this economically important disease of pigs.

Applications and Advantages

Offers alternative cell culture systems to develop next generation of vaccines against PRRSV

IP Status

US and PCT patent applications pending

Publication

PCT Publication No. WO 2008109237A2

US Publication No. US-2010-0146653-A1

Abstract

Bovine tuberculosis (TB) and Johne’s disease are economically important diseases of ruminants. Bovine tuberculosis is caused by Mycobacterium bovis (Mbv), while Johne’s disease is caused by M. avium subsp. Paratuberculosis (Map.). According to the Agricultural Research Service of the USDA, Johne’s disease costs the U.S. dairy industry about $200 million a year in reduced milk production and there are additional costs due to early culling of animals. Bovine TB, one of three types of TB (human, avian, and bovine), can infect all warmblooded vertebrates. The lack of diagnostic tests to detect infected animals early in the course of disease combined with the lack of effective vaccines make controlling these diseases is difficult.

WSU inventors have adapted and improved an allele exchange technique for creating mutant strains of mycobateria, creating a disruption in a selected gene. This improved efficiency of gene disruption has provided an opportunity to target genes essential for in vivo survival of the bacteria. Specifically, the research team used the technique to successfully develop two mutants for Mbv and three for Map. Studies are currently in progress with the Map mutants to show they elicit protective immunity, which could then be used as vaccines.

Applications and Advantages

Provides opportunity to develop better vaccines and improved diagnostic kits for bovine tuberculosis and John’s disease.

IP Status

US, Mexico and Canada patent applications pending                                         

Publication

PCT Publication No. WO 2009009798

Park, Kun Taek, Dahl, John, Bannantine, John P. , Barletta, Rau´l G. ,  Ahn, Jongsam, Allen, Andrew J. , Hamilton, Mary Jo, and Davis, William. 2008. Demonstration of Allelic Exchange in the Slow-Growing Bacterium Mycobacterium avium subsp. paratuberculosis, and Generation of Mutants with Deletions at the pknG, relA, and lsr2 Loci. Applied and Environmental Microbiology 74(6): 1687-1695

Abstract

For many years silver has been used as a broad spectrum antimicrobial agent, applied towards reducing infections of burn victims, water treatment, treating textiles, among others. With an increasing amount of antibiotic-resistant bacteria, the utility of silver coatings and treatments are again being recognized as a cost- effective way to prevent bacterial infections such as for medical implants. This is especially crucial when surgeries are performed in environments where sanitation is not ensured.

This WSU invention relates to the use of silver coatings on medical implants as a valuable addition to promote antimicrobial properties such as resistance to growth of Gram negative bacteria (e.g., Pseudomonas aeruginosa). In an effort to optimize antimicrobial effectiveness and keep human cell-toxicity to a minimum, WSU inventors have experimented with various coating parameters and observed their effects on the utility of silver coating on SIGN stainless steel implants.

Applications and Advantages

Silver deposited implants offer to reduce growth of infection due to biofilm formation and aid fracture healing.

IP Status 

US patent application pending

Abstract

Low density, low stiffness load-bearing implant structures are a dream for orthopedic surgeons. In total hip replacements (THR), dense metals with high density, high stiffness, and strength than natural bone is traditionally used as implant to replace the diseased or damaged hip, and help restore the natural hip function of the patient. Typical lifetime of a THR, however, is only seven to twelve years, and this lifetime has remained constant over the past 50 years. Low density and low stiffness implants are believed to increase the lifetime of THRs and researchers through time have attempted to produce natural bone-like properties implants but failed in most cases.  

Using metal-based rapid prototyping process, WSU inventors have developed a process to create functional load-bearing implants yet low density and low stiffness. Our inventors have reduced the overall stiffness and weight of the implants to 30-50% without changing its composition, size, and shape. The process they have developed can also be modified to add surface porosity for better biological fixation/bonding.

Applications and Advantages

■  Reduced stiffness and weight. Stiffness and weight reduced by 50% or more without changing the implant composition, size or shape.

■ Further aspects of this design optimize the implants' compositional similarities with natural bone:

- Improved biological fixation. The addition of calcium phosphates to create compositionally gradient porous structures enables tissue to grow through the pores and bond significantly better compared to any dense implants;

- Increased surface bioactivity. Nano-porous TiO2 surface modifications are applied via an intelligent modification approach which optimizes cell-materials interactions for early stage cell adhesion and proliferation.

IP Status

US patent application

Abstract

Bronchoscopy allows for the evaluation of the trachea (windpipe), carina (sensitive area within the trachea), and bronchi of an animal patient.  General anesthesia is required for bronchoscopy to suppress coughing and laryngospasm and to allow for examination of the airway without inducing trauma.

To perform a veterinary bronchoscopy, the standard procedure is to disconnect the anesthetized patient from oxygen and anesthesia and insert a flexible endoscope down the airway for evaluation purposes.  Once the patient’s blood oxygen saturation falls below 80%, the endoscope must be removed and the oxygen/anesthesia reconnected to the patient.  Once the patient’s blood oxygen saturation levels have recovered, the whole process of disconnecting the oxygen/anesthesia and reinserting the endoscope begins again.  This process continues until the exam is completed.

One alternative is to supply oxygen to the patient through the endoscope’s biopsy channel, if the endoscope is so equipped.  This will extend the examination time from seconds to minutes.  However, using this approach can result in excessive oxygen flow to the patient, which can result in rupture of alveoli or even pneumothorax (collapsed lung).  The BGTG is a novel device that allows a complete exam while maintaining proper blood oxygen saturation levels without having to remove the endoscope and interrupt the exam.  Examination times are significantly reduced using the BGTG device.

Applications and Advantages

This low cost-device allows bronschocopy while administering oxygen/anesthesia and maintaining oxygen saturation throughout the procedure.

IP Status

US Patent Application No. 61/271,684

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.

IP Status

Patent pending in US.                 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages 

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.  

IP Status

Patents issued in: US (6,114,160; 6,610,527)

Abstract

Inserting feeding tubes into animal patients during esophagostomy procedures (insertion through the neck to the esophagus) can be difficult.  Scarring and other tissue damage can occur if the procedure is done incorrectly.  A special feeding tube insertion device developed at WSU can be used to simplify the procedure making it safer and quicker to accomplish with minimal discomfort to the animal.

Applications and Advantages

■  Decreases risk to animals during surgery

■  Reduce time of procedure to 5 minutes

■  Saves money (use of anaethesia and personnel)

■  Easy to use

IP Status

US Patent No. 61/292,960

Abstract

Artemisinin, a product of the qinghaosu plant (Artemisia annua L.) has long been used as a natural antimalarial remedy, and currently been reported to treat human cancer. Artemisinin, like most chemotherapeutic compounds, works by the production of free radicals inside cancer cells but are more selective in action and produce significantly fewer side effects.

WSU researchers discovered ways on how to further boost the effectiveness of artemisinin as a natural cancer remedy, such as for leukemia. Specifically, the focus was to enhance artemisinin's effects on cancerous cells through hyperbaric oxygen therapy, which is used for decompression sickness, carbon-monoxide poisoning, Lyme disease and slow-to-heal wounds. Results of in vitro experiments confirmed anticancer activity of artemisinin and hyperbaric oxygen as single agents. Using them in combination resulted in an additional 22% decrease in cells' growth, which supports that an increase in oxygen tension enhances effectiveness of artemisinin.

Applications and Advantages

Combined artemisinin and hyperbaric oxygen therapy offers a new chemotherapeutic regimen strategy for cancer treatment in humans and animals, with effectiveness increased over that of artemisinin or hyperbaric oxygen therapy alone. Other promising applications of this combination include anti-inflammatory and anti-angiogenesis therapy.

IP Status

Available for licensing

Publication

Ohgami Y, Elstad CA, Ching E, Shirachi DY, Quock RM and Lai H. (2010). Effect of hyperbaric oxygen on the anticancer effect of artemisinin on Molt-4 human leukemia cells. Anticancer Research 30: 4467-4470

Abstract

Our research team has demonstrated that recombinant protein can be synthesized and secreted directly into the supernatant. The novelty of this invention is that the 5’ end of potentially any Type III secreted protein can be used to drive the export of a recombinant protein from a bacterial cell. Likewise, although this platform was tested for Campylobacter, the technology is versatile enough to be used for: a) production of other vaccines; and b) enable expression of difficult-to-express proteins because of cell toxicity type issues. In this latter case, the expression is facilitated because of the system’s ability to shunt proteins into the supernatant and not retain them within the cell.  This feature makes it easier also to purify the expressed protein.

Applications and Advantages

Offers a versatile method enough to be used for (a) production of other vaccines; and (b) expressing difficult-to-express proteins because of cell toxicity type issues

IP Status  

US patent application pending

Publication(s)

Neal-McKinney, J.M., Christensen, J.E., and M.E. Konkel. 2010. Amino-terminal residues dictate the export efficiency of the Campylobacter jejuni filament proteins via the flagellum. Molecular Microbiology. Mol Microbiol. 76(4). 918-931

Christensen, J.E., Pacheco, S.A., and M.E. Konkel. 2009.Identification of a Campylobacter jejuni-secreted protein required for maximal invasion of host cells. Mol Microbiol 73(4). 650-662

Abstract

This invention relates to methods to engineer biomimetic vectors with chimeric architecture for targeted gene therapy. WSU inventor has engineered a multi-domain biomacromolecule using a novel technique and identified the structure of a vector where the functional propensity of the concept biomacromolecule is scripted into the primary sequence structure to perform an array of self-guided functions. These include: a) efficient condensation of the plasmid DNA into deliverable nanoparticles by adenovirus mu peptide, b) delivery of the nanoparticles to model breast cancer cells using a combinatorially screened cyclic targeting peptide (TP) [1], c) endosomal disruption using a synthetic fusogenic peptide (FP) facilitating escape of the cargo into cytosol, and finally d) localization of the gene in the nucleus by HIV nuclear localization signal (NLS). By shuffling the order of the functional domains, a library of the DNA transporters was genetically engineered to screen the active candidate with the optimum sequence for a purpose. This method/technique is applicable to any type of molecule (DNA/peptide/RNA/siRNA, etc. ) with any number of elements in the vector and can be adapted to many purposes.

Applications and Advantages

Offers a biomimetic vector for efficient and targeted gene transfer.

IP Status 

US patent application pending

Publications

B.F. Canine, Y. Wang, A. Hatefi. 2009. Biosynthesis and characterization of a novel genetically engineered polymer for targeted gene transfer to cancer cells. J Control Release  138(3) : pp 188-196

S.S. Mangipudi, B.F. Canine, Y. Wang, A. Hatefi. 2009. Development of a Genetically Engineered Biomimetic Vector for Targeted Gene Transfer to Breast Cancer Cells. Mol. Pharmaceutics 6 (4): 1100–1109 .

Y. Wang, S.S. Mangipudi, B.F. Canine, A. Hatefi. 2009. A designer biomimetic vector with a chimeric architecture for targeted gene transfer. J Control Release  137(1): 46-63

Abstract

When a colonoscopy is preformed on a subject the colon is first insufflated with a gas to expand the internal chamber.  Often, air escapes through the anal sphincter, thus, requiring a manual compression of the sphincter for the duration of the examination.  WSU inventors have developed a gas-tight endoscope guide -- a plastic device for guiding the endoscope and creating a gas-tight barrier between the animal patient and the operator during colonoscopy procedures.  The gas-tight guide prevents the passage of gases, secretions, and fluids during the procedure thus reducing the risk of complications.

Applications and Advantages

This low cost-device allows bronschocopy while administering oxygen/anesthesia and maintaining oxygen saturation throughout the procedure.

IP Status

US Patent No. 61/271,706

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.

IP Status  

Patents issued in: US (6,610,527; 5,994,114);  France, Europe, United Kingdom, Switzerland, and Spain (0907312); Italy (26217/BE/2006);  Germany (DE 69735419) ; Canada (2,250,693) ; Australia (710405)

Several others pending.   

Publications

Jennewin, Stefan; Rithner, Christopher; Willliams, Robert; and Croteau, Rodney. Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase. PNAS (2001), 98(24), 13595-13600

Jennewein, Stefan; Wildung, Mark; Chau Mydoanh; walker, Kevin, and Croteau, Rodney. Random sequencing of an induced Taxus cell cDNA library for identification of clones involved in Taxol biosynthesis . PNAS (2004), 101(24), 9149-9154 .

Abstract

These WSU technologies relate to reducing the incidence of C. jejuni bacteria infections in poultry and in humans, and more particularly to novel antigenic 5 compositions, vaccines, and methods for generating an immune response against C. jejuni bacteria in an animal.

Our research team has identified 30 “best-fit” antigenic composition or immunogenic membrane-associated C. jejuni proteins. These antigenic compositions are potentially valuable vaccine candidates that can be orally administered through the bird’s water or food supply. In research trials, these antigenic compositions have significantly reduced the pathogen's ability to colonize young chickens' intestines, where the infection begins. These technologies and methods could provide an effective alternative to antibiotics the poultry industry uses to control these pathogenic bacteria.

The methods developed for Campylobacter are, however, versatile enough to be used for (a) production of other vaccines; and (b) expressing difficult-to-express proteins because of cell toxicity type issues. In this latter case, the expression is facilitated because of the system’s ability to shunt proteins into the supernatant and not retain them within the cell.  This feature makes it easier also to purify the expressed protein.

Campylobacter jejuni is now the No. 1 food-borne pathogen in the United States and the world, surpassing Salmonella. In the United States alone, 2.4 million cases are reported annually, with with an estimated cost of treatment and loss of productivity of $8 billion annually. Humans are frequently infected with C. jejuni by handling or consuming raw poultry products. 

Applications and Advantages

Offers novel vaccine candidates and methods to generate immune response against Campylobacter jejuni in chickens, and other avian species.

IP Status 

US patent application pending

Publication                          

Shoaf-Sweeney, K.D., Larson, C.L., Tang, X., and M.E. Konkel. Identification of Campylobacter jejuni proteins recognized by chicken maternal antibodies.  Appl. Environ. Microbiol. 74:6867-6875, 2008

Konkel, M.E., Larson, C.L., and R.C. Flanagan. The food-borne pathogen Campylobacter jejuni synthesizes a novel fibronectin-binding protein termed FlpA that facilitates adherence to human epithelial cells. J. Bacteriol. 192:68-76, 2010.

Flanagan, R.C., Neal-McKinney, J.M., Dhillon, A.S., Miller, W.G., and M.E. Konkel.  Examination of Campylobacter jejuni putative adhesins leads to the identification of a new protein, designated FlpA, required for chicken colonization.Infection and Immunity. 77(6):2399-407, 2009 

Abstract

Mannheimia (Pasteurella) haemolytica is the most important bacterial pathogen of respiratory disease in cattle, sheep, and other domestic and wild ruminants. This bacterial pathogen produces leukotoxin, which kills the white blood cells, and, hence is primarily responsible for bronchopneumonia and death in ruminants. Pneumonic diseases cause huge economic losses to the cattle and sheep industries worldwide.

WSU has a strong research program focused on understanding the pathogenesis of animal diseases such as pneumonia caused by M. haemolytica and developing effective and cost-efficient control and preventive measures against this pathogen.  A team of WSU veterinary microbiologists and pathologists recently found that the growth and colonization of the M. haemolytica can be inhibited using another bacterial species by a contact dependent mechanism, a phenomenon recently found among Escherichia coli strains. This team had isolated leukotoxin-negative Bibersteinia trehalosi(inhibitor) to inhibit the growth of M. haemolytica (target). B. trehalosiis also one of the most common bacterial isolates that cause pulmonary diseases in ruminants (especially in big sheep horns), with only 15 percent of the strains producing leukotoxin. Although the two bacterial species are closely related on the family tree and cultured in close proximity to each other, studies by WSU experts showed that “horizontal gene transfer” did not happen, hence, the isolated B. trehalosi strains are free of leukotoxin gene found in M. haemolytica.

Applications and Advantages

The isolated B. trehalosi strains can be used as nasal spray to eliminate M. haemolytica that are present as commensal bacteria in the nasopharynx of cattle, domestic sheep and other ruminants.

IP Status

Available for licensing

Abstract

WSU pioneered another research focused on a genome-wide association study to identify loci putatively associated with tolerance to bovine tuberculosis, an economically important infectious disease in cattle. Bovine paratuberculosis, commonly referred to as Johne's disease, is a contagious bacterial disease estimated to be present in over 65% of US dairy herds and results in annual losses in the hundreds of millions of US dollars. Mycobacterium avium subspecies paratuberculosis (MAP) is the bacteria responsible for Johne's disease. 

WSU researchers did the whole genome association analysis using BovineSNP50 BeadChip, and identified multiple single nucleotide polymorphisms (SNPs) associated with Johne's disease after stringent multiple testing correction. The SNPs identified as being associated with tolerance to/infection with MAP included previously unreported regions on chromosome 1 and the X chromosome.

Tolerance, which indicates the fitness of the hosts at a given level of tissue infection, represents a new way of evaluating the impact of disease on animals and a new means of marker assisted selection for carcass and health traits in cattle.  Selection of animals for tolerance would put different pressures on the host (cattle) and the pathogen (MAP) and can be an effective means of controlling this disease than selection for disease resistance.

Applications and Advantages

■   Selection of tolerant animals that are less harmed by MAP infection, reducing the transmission of MAP to other animals in the herd, and improving profitability in cattle.

IP Status

US patent application filed

Publication

R. Zanella,  M. L. Settles, S. D. McKay, R. Schnabel,  J. Taylor, R. H. Whitlock, Y. Schukken, J. S. Van Kessel,  J. M. Smith, H. L. Neibergs. 2010. Identification of Loci Associated with Tolerance to Johne’s Disease in Holstein Cattle. Animal Genetics. pp  1- 11.

US-2010-0223687-A1

Abstract

WSU pioneered another research focused on a genome-wide association study to identify loci putatively associated with tolerance to bovine tuberculosis, an economically important infectious disease in cattle. Bovine paratuberculosis, commonly referred to as Johne's disease, is a contagious bacterial disease estimated to be present in over 65% of US dairy herds and results in annual losses in the hundreds of millions of US dollars. Mycobacterium avium subspecies paratuberculosis (MAP) is the bacteria responsible for Johne's disease. 

WSU researchers did the whole genome association analysis using BovineSNP50 BeadChip, and identified multiple single nucleotide polymorphisms (SNPs) associated with Johne's disease after stringent multiple testing correction. The SNPs identified as being associated with tolerance to/infection with MAP included previously unreported regions on chromosome 1 and the X chromosome.

Tolerance, which indicates the fitness of the hosts at a given level of tissue infection, represents a new way of evaluating the impact of disease on animals and a new means of marker assisted selection for carcass and health traits in cattle.  Selection of animals for tolerance would put different pressures on the host (cattle) and the pathogen (MAP) and can be an effective means of controlling this disease than selection for disease resistance.

Applications and Advantages

■   Selection of tolerant animals that are less harmed by Map infection, reducing the transmission of Map to other animals in the herd, and improving profitability in cattle.

IP Status

US patent application filed

Publication

R. Zanella,  M. L. Settles, S. D. McKay, R. Schnabel,  J. Taylor, R. H. Whitlock, Y. Schukken, J. S. Van Kessel,  J. M. Smith, H. L. Neibergs. 2010. Identification of Loci Associated with Tolerance to Johne’s Disease in Holstein Cattle. Animal Genetics. pp  1- 11

US-2010-0223687-A1

Abstract

The invention relates to implant for total hip replacements or fixing physical hip joints damage. Using metal-based rapid prototyping process, WSU inventors have developed a process to create functional load-bearing implants yet low density and low stiffness.

Low density, low stiffness load-bearing implant structures are a dream for orthopedic surgeons.  In total hip replacements (THR), dense metals with high density, high stiffness, and strength than natural bone is traditionally used as implant to replace the disease or damaged hip and help restore the natural hip function of the patient. Typical lifetime of a THR, however, is only seven to twelve years, and this lifetime has remained constant over the past fifty years. Low density and low stiffness implants are believed to increase the lifetime of THRs and researchers through time have attempted to produce natural bone-like properties implants but failed in most cases. Our inventors have reduced the overall stiffness and weight of the implants to 30-50% without changing its composition, size, shape. The process they have developed can also be modified to add surface porosity for better biological fixation/bonding.

Applications and Advantages

■  Reduced stiffness and weight. Stiffness and weight reduced by 50% or more without changing the implant composition, size or shape.

■  Further aspects of this design optimize the implants' compositional similarities with natural bone:

1.    Improved biological fixation. The addition of calcium phosphates to create compositionally gradient porous structures enables tissue to grow through the pores and bond significantly better compared to any dense implants.

2.    Increased surface bioactivity. Nano-porous TiO2 surface modifications are applied via an intelligent modification approach which optimizes cell-materials interactions for early stage cell adhesion and proliferation.

IP Status 

US and Indian patent applications pending.

Publications

US Patent Publication No. 2007-0203584 A1

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/ lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants: enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,635,459; 6,210,942), Australia (728116) and several others pending. 

Abstract

This WSU invention is a method for detecting prion protein (also denoted as PrP-Sc protein) as an indicator of transmissible spongiform encephalopathies. This method relates to non-invasive, preclinical methods for detection of prion proteins in ruminants using third eyelid lymphoid tissue. The invention further relates to monoclonal antibodies that specifically bind a conserved epitope of prion proteins in ruminants and immunoassays using the antibodies to detect prion protein in fixed, treated tissue.

Applications and Advantages

■   Provides a practical, inexpensive, non-invasive method for detecting PrP-Sc in live animals and sensitive immune-histochemical assays to detect PrP-Sc in animal tissues and animal by-products.

IP Status 

US Patent (6,165,784; 6,514,707) ; New Zealand (503875); Australia (756955);
PCT and Europe patent applications pending

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.                                                                  

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production. 

Abstract

     Harmful strains of Eschiricia coli bacteria, primarily found in cattle cause severe, sometimes life-threatening human illness. According to the US’ Centers for Disease Control and Prevention, an estimated 110,000 cases (due to specifically enterohaemorrhagic E. coli (EHEC)) occur annually in the United States, and is now plaguing more than 30 countries around the globe. The other E. coli virotype, enterotoxigenic E. coli (ETEC), according to the World Health Organization, causes more than 200 million cases of diarrhea and 380,000 deaths, mostly in children in developing countries.

     Typically, growth and division of these bacteria are inhibited using antibiotic drugs, which interfere with bacterial metabolic processes. Heavy use of antibiotics, however, resulted to drug-resistant forms of E. coli. Bacterial contact inhibition offers new way to interfere with bacterial growth and growth arrest. Current contact-dependent inhibition mechanisms, however, have a narrow target range. More importantly, the route of infection to humans is via contaminated meat where there is a zero tolerance policy in place. This in turn necessitates removal of the harmful bacteria before cattle enter the slaughterhouse.

     A team of WSU veterinary microbiologists and pathologists have discovered a novel inhibition mechanism that is effective against diverse panel of E. coli, including E. coli O157:H7 and can be exploited to further control or prevent colonization of cattle by E.coli virotypes in humans, livestock, and poultry. The team has identified a proximity-dependent inhibition phenotype of E.coli, expressed when E-coli strains are co-cultured in defined minimal media. The inhibitory activity was specifically found effective against 13 diverse panel of E.coli strains, including EHEC, ETEC, multi-drug resistant and commensal E.coli, among a few. The strains expressing the inhibitory phenotype are likewise immune to inhibition by other inhibitor strains.

Applications and Advantages

■  The effectiveness of our inhibitory mechanism offers great potential for dipstick type application to cattle prior to their entry into slaughterhouse.

■  Discovery is novel and unique from all recognized contact-based inhibition mechanisms; and

■  Inhibition mechanism has broad spectrum activity that includes E. coli strains pathogenic to both humans and animals and shows reduction by at least five logs.

IP status

Available for licensing

Publication

Sawant, A., Casavant, N. C., Call, D., & Besser, T. (2011). Identification and Characterization of Proximity-Dependent Inhibition in Eschirichia coli Isolated from Cattle. Applied and Environmental Microbiology, 2345-2351.

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.         

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants:    enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,210,942; 6,635,459) and several others pending.           

Abstract

This invention relates to nucleic acid sequences which code for pinoresinol/lariciresinol reductases from Forsythia intermedia and Thuja plicata, and to vectors containing the sequences, host cells containing the sequences and methods of producing recombinant pinoresinol/lariciresinol reductases and their mutants. Pinoresinol and lariciresinol are more recently identified plant lignans, a structurally diverse group of plant natural products that have diverse properties. The complex lignan biopolymers contribute to the structure of the woody parts of plants such as the heartwood while the less complex lignans possess medicinal and nutraceutical properties. Genetically improved plants with high levels of desirable lignans can be consumed directly, or the desirable lignans can be purified from the plants to yield a dietary supplement.

Applications and Advantages

The presence of genes encoding enzymes involved in the biosynthesis of one or more classes of lignans permits genetic improvement of plants:  enhance wood quality in trees; and increase synthesis of one or more types of lignans with desirable pharmacological properties.

IP Status

Patents issued in: US (6,911,330); New Zealand (508270) and several others pending. 

Abstract

This invention utilizes SiRNAs that target mRNA transcripts to down-regulate the expression of peptide products encoded by the preproghrelin gene.  Further information about the effects of the decreased gene expression enables the better understanding of the physiological role of preproghrelin gene products, ghrelin and obestatin, in the regulation of food intake, body weight, thermo-, and sleep regulation.  Previous studies showed that ghrelin is involved in the short- and long-term regulation of energy balance by stimulating feeding and suppressing energy expenditure while obestatin suppresses food intake and body weight gain in mice.  Ghrelin and obestatin are also implicated in sleep regulation.  Sleep deprivation induces increases in hypothalamic and plasma ghrelin levels.  In rats, administration of ghrelin facilitates wakefulness whereas injection of obestatin promotes sleep.

Using transgenic mice as models, WSU inventors characterized sleep and thermo-regulatory responses to food deprivation in cold environment of mice lacking the preproghrelin gene and in a separate experiment, in mice that lack functional ghrelin receptors. Following were the results of our experiments:

1.    Normal mice when exposed to food deprivation at low ambient temperature generated hypothermic bouts (1-5°C decrease in body temperature) accompanied by characteristics metabolic and sleep-wake activity changes.

2.    Mice lacking the preproghrelin gene showed increased sensitivity to the same metabolic challenge.  These mice first entered mild hypothermic bouts, associated with severely reduced sleep which followed by a marked drop in body temperature to near ambient temperature levels.

3.    Mice that lack functional ghrelin receptors showed responses similar to those observed in normal mice when challenged by the same conditions.

4.    Products of the preproghrelin gene are required for maintaining the normal sensitivity to metabolic challenges and coordinated regulation of metabolism and sleep in mice.

Our data provide further insight into the coordinated regulation of metabolism, thermoregulation and sleep.  Regulated hypothermia can be utilized to decrease metabolism during prolonged surgeries, preserve organs before transplantation and also to improve survival of humans during trauma. This research also has high potentials for developing preventive/therapeutic agents for obesity in humans. For example, SiRNAs that inhibit the transcription of the peptide products encoded by the preproghrelin gene or ghrelin antagonists may facilitate weight loss, decrease appetite and to help maintaining normal body weight.  Additional research, however, is needed to realize these objectives.

Applications and Advantages

Have applications in body temperature control and also in the area of obesity  using siRNAs, peptides, etc.

IP Status 

US patent application pending

Publications

US Patent App No. US-2010-0196396-A1

Eva Szentirmai, Levente Kapas, Yuxiang Sun, Roy G. Smith, and James M. Krueger. 2007. Spontaneous sleep and homeostatic sleep regulation in ghrelin knockout mice. Am J Physiol Regul Integr Comp Physiol 293: R510–R517,

Eva Szentirmai, Levente Kapas, and James M. Krueger. 2007. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats Am J Physiol Regul Integr Comp Physiol 292: R575–R585.

Eva Szentirmai, Levente Kapas, Yuxiang Sun, Roy G. Smith,and James M. Krueger. 2009. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. PNAS 106 ( 33): 14069–14074

Abstract

Laparoscopic surgery is a minimally invasive surgical technique.  This procedure has traditionally required insufflating the abdominal cavity with gas to crate sufficient space to insert and maneuver surgical tools.  However, the gas pressure associated with such insufflations can have deleterious consequences on blood pressure and lung inflation.  Gasless laparoscopy avoids gas pressure on intra-abdominal blood vessels and on the diaphragm.  This procedure is especially advantageous in patients with already compromised cardiovascular or pulmonary function.  Gasless laparoscopy has been developed for humans but found unsuitable for optimal use in canine and feline abdominal surgery.  To our knowledge, gasless laparoscopy has not been reported in small animal surgery.

This invention offers an abdominal retractor suitable for use in animal gasless laparascopy.  Traction is produced by threading a suspension rod perpendicularly through the loop at the end of the retractor.  The suspension rod is then connection to a traction device.  Once connected, traction is applied to the retractor to “tent up” the abdominal cavity hence creating ample space for the insert and maneuvering of surgical instruments.

Applications and Advantages

This abdominal retractor enables the veterinary surgeon to perform laparoscopic surgery (key-hole surgery) without insufflating the cavity with gas for the safe insertion of instrumentation into the abdomen.

IP Status

Not patented

Abstract

This invention deals with surface modification of implants.  More specifically, it focuses on the simultaneous improvement of bone cell materials interactions and anti-microbial activity.  The results focus on surface treatment methods to simultaneously enhance tissue integration while reducing chances of infection that can be applied as a post-processing operation to metallic implants such as hip, knee, and spinal devices as well as screws, pins, and plates.

Applications and Advantages

■   Offers to enhance cellular adhesion and promote growth of natural bone cells while preventing microbial activities

■   Reduces need for antimicrobial medications post surgery

IP Status 

US patent application pending, FDA approval pending (trials underway)

Abstract

M. haemolytica is the most important bacterial pathogen of respiratory disease in cattle and other domestic and wild ruminants. This disease, commonly known as pneumonic pasteurellosis or shipping fever in cattle, has been estimated to cost  US $1 billion to the cattle industry of the United States alone. Leukotoxin (Lkt)-induced polymorphonuclear leukocytes (PMN) lysis and degranulation are the primary causes of acute inflammation and lung injury characteristic of pneumonic pasteurellosis.

WSU research team previously identified β₂ integrins as the receptor for Lkt on bovine leukocytes. Subsequently, they have also discovered that Lkt uses CD18 as its receptor on the leukocytes of domestic sheep and bighorn sheep which are also susceptible to pneumonia caused by M. haemolytica. The Lkt binding domain was found to lie between amino acids 1-291 of the CD18 molecule of bovine leukocytes. Based on this amino-acid sequence, synthetic peptides have been developed that effectively inhibit Lkt-induced cytolosis of neutrophils and other leukocytes of cattle. Inhibition of Lkt- induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino-acids 5-17 of CD189, which, surprisingly, comprise most of the amino acids of the signal peptide that remains intact on mature CD18 molecules on the cell surface. The failure of the signal peptide to be cleaved from mature CD18 molecules renders the ruminant leukocytes susceptible to Lkt. These important discoveries, therefore, would enable the cloning of domestic and wild ruminants resistant or much less suceptoble to the lethal effects of pneumonic pasteurollosis thus preventing concomitant economic losses.

Applications and Advantages

Offers the precise binding site of leukotoxin, the most important virulence factor produced by Mannheimia haemolytica on its leukocyte receptor bovine CD18. This finding lends itself to creating vaccines for shipping fever as well as cloning cattle that are resistant to Mannheimia haemolytica.

IP Status 

US and PCT applications pending    

Publication

Shanthalingam, Sudarvili and Srikumaran, Subramaniam. 2009. Intact signal peptide of CD18, the β-subunit of β₂-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin. PNAS 106 (36): 15448-15453

Abstract

This WSU invention relates to mesoporous calcium silicate compositions and methods for producing mesoporous calcium silicate for controlled release of bioactive agents (i.e. proteins, growth factors, pharmaceutical drugs, antibiotics, polypeptides, etc.).  Using hydrochloric acid at different pH, mesoporous calcium silicate was synthesized by acid modification of wollastonite. A hydrated silica gel with abundant Si-OH functional group was formed on the surface. Bruhauer-Emmettt-Teller (BET) surface area increased significantly due to acid modification and reached over 350 m²/g. Acid modified mesoporous calcium silicate particles demonstrate an increased ability to adsorb protein compared to unmodified calcium silicate particles, and further demonstrate controlled release kinetics of these proteins.

Applications and Advantages

■  Offers calcium silicate materials for use in bone implant applications with increased bioactivity and bioactive agent loading.

IP Status 

US patent application pending

Abstract

M. haemolytica is the most important bacterial pathogen of respiratory disease in cattle and other domestic and wild ruminants. This disease, commonly known as pneumonic pasteurellosis or shipping fever in cattle, has been estimated to cost  US $1 billion to the cattle industry of the United States alone. Leukotoxin (Lkt)-induced polymorphonuclear leukocytes (PMN) lysis and degranulation are the primary causes of acute inflammation and lung injury characteristic of pneumonic pasteurellosis.

WSU research team previously identified β₂ integrins as the receptor for Lkt on bovine leukocytes. Subsequently, they have also discovered that Lkt uses CD18 as its receptor on the leukocytes of domestic sheep and bighorn sheep which are also susceptible to pneumonia caused by M. haemolytica. The Lkt binding domain was found to lie between amino acids 1-291 of the CD18 molecule of bovine leukocytes. Based on this amino-acid sequence of the Lkt-binding domain on CD18, synthetic peptides have been developed that effectively inhibit Lkt-induced cytolosis of neutrophils and other leukocytes of cattle. Inhibition of Lkt- induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino-acids 5-17 of CD189, which, surprisingly, comprise most of the amino acids of the signal peptide that remains intact on mature CD18 molecules on the cell surface. The failure of the signal peptide to be cleaved from mature CD18 molecules renders the ruminant leukocytes susceptible to Lkt. These important discoveries, therefore, would enable the cloning of domestic and wild ruminants resistant or much less susceptible to the lethal effects of pneumonic pasteurollosis, thus, preventing concomitant economic losses.

Applications and Advantages

Offers the precise binding site of leukotoxin, the most important virulence factor produced by M. haemolytica on its leukocyte receptor bovine CD18. This finding lends itself to creating vaccines for shipping fever as well as cloning cattle that are resistant to M. haemolytica.

IP Status 

US and PCT applications pending    

Publication

Shanthalingam, Sudarvili and Srikumaran, Subramaniam. 2009. Intact signal peptide of CD18, the β-subunit of β₂-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin. PNAS 106 (36): 15448-15453

International Publication No. WO 2010/088691 A2

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production.

IP Status

Patents issued in: US (6,073,072), Australia (763368) and several others pending.           

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives.

■  Provides a potentially cheaper method of production.            

IP Status

Patents issued in: US (7,153,676) and several others pending.  

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production. 

IP Status

US Patent No. 6,818,755 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives.

■  Provides a potentially cheaper method of production.           

IP Status

Patents issued in: US (6,287,835), Japan (3730918), Europe (00967189.2), Canada (2,387,971), and several others pending. 

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.         

Applications and Advantages 

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives;

■  Provides a potentially cheaper method of production. 

IP Status

Patent pending in US.

Abstract

The anticancer drug Paclitaxel is in short supply.  Paclitaxel, and its derivatives that are being discovered, are regularly being shown to be effective in treating malignancies. The only commercially viable sources of paclitaxel and its generic equivalents (and their precursors for semi-synthesis) are the bark and needles of yew species. This technology could provide a cheaper, more reliable, alternative method that does not rely on a large and continuous supply of bark or needles for producing paclitaxel or its precursors for semi-synthesis as well as a way to produce the precursors for developing second generation drugs.  The inventors isolated many of the genes encoding enzymes that catalyze the slow steps of the complex pathway.  Improving the yield of Paclitaxel and related metabolites by manipulating these genes should provide alternative methods of producing paclitaxel and other intermediates used in semi synthesis.

Applications and Advantages 

■  Provides an alternative method of producing taxol or the intermediates for semi synthesis of taxol or new derivatives.

■  Provides a potentially cheaper method of production.         

Abstract

This device is intended to assist in the procedure for the placement of urinary catheters into female canines, which can be problematic given the flared end of catheters, which are too large to allow the standard otoscope speculum to be removed until the catheter is removed from the patient.  Our device enables the speculum to be removed once the catheter is in place.

Applications and Advantages

This invention allows for the effective removal of the speculum which can get in the way of the operation.

IP Status

US patent application under consideration

Abstract

These WSU technologies relate to reducing the incidence of C. jejuni bacteria infections in poultry and in humans, and more particularly to novel antigenic 5 compositions, vaccines, and methods for generating an immune response against C. jejuni bacteria in an animal.

Our research team has identified 30 “best-fit” antigenic composition or immunogenic membrane-associated C. jejuni proteins. These antigenic compositions are potentially valuable vaccine candidates that can be orally administered through the bird’s water or food supply. In research trials, these antigenic compositions have significantly reduced the pathogen's ability to colonize young chickens' intestines, where the infection begins. These technologies and methods could provide an effective alternative to antibiotics the poultry industry uses to control these pathogenic bacteria.

The methods developed for Campylobacter are, however, versatile enough to be used for (a) production of other vaccines; and (b) expressing difficult-to-express proteins because of cell toxicity type issues. In this latter case, the expression is facilitated because of the system’s ability to shunt proteins into the supernatant and not retain them within the cell.  This feature makes it easier also to purify the expressed protein.

Campylobacter jejuni is now the No. 1 food-borne pathogen in the United States and the world, surpassing Salmonella. In the United States alone, 2.4 million cases are reported annually, with with an estimated cost of treatment and loss of productivity of $8 billion annually. Humans are frequently infected with C. jejuni by handling or consuming raw poultry products. 

Applications and Advantages

Offers novel vaccine candidates and methods to generate immune response against Campylobacter jejuni in chickens, and other avian species.

IP Status 

US patent application pending

Abstract

Four hybrid poplar clones representing up to 4 age classes (sizes) were measured for height, diameter, and tree biomass (stems, branches, stumps, and roots).  All of the biomass components were analyzed for carbon content and aboveground (stem + branches), belowground (stumps + roots) and total (aboveground + belowground) carbon content were calculated for each tree representing 4 clones, 4 age classes, and 2 biographical areas (east and west of the Cascade Mountains).  An estimate of stem volume for each tree was determined using the equation:  volume = height x diameter x diameter.  Predictive equations were developed using linear regression methods that relate tree volume to aboveground, belowground, and total tree carbon .  The equations are provided on the attached sheets both in English units (cubic feet and pounds) and metric units (cubic meters and kilograms).  Equations were generated based on combined data (all clones and all sites), combined eastside (clones of 184-411, 52-225, and OP-367 all located near Boardman, Oregon), combined westside (clones 15-29 and one age class of 52-225 located near Salem, Oregon), individual clones, and for 52-225, eastside only and eastside and westside combined.  In addition to the slope and intercept values from the regression analysis, the coefficients of determination (R squared) are provided for each equation.  This parameter is an estimate of how well the equation fits the data, with 1.00 being a perfect fit.  With biological entities, any value above 0.75 is usually considered a good fit. 

Abstract

Beyond the traditional voltage security assessment methods like V-P curve and Q-V curve, this invention provides a novel concept and a fast computation method based on power flow to indicate a global voltage security assessment index. Build on the understanding of line sensitivity, this kind of index is able to describe the current system operation status and mark the weakest bus.

Applications and Advantages

■   Offers a simple and fast computation method yet based on power flow analysis;

■   Does not require plenty of power calculation;

■   Offers real-monitoring, load margin estimation, and prevent system voltage collapse; 

IP Status 

US patent application(s) pending

Abstract

The present invention relates to a new apparatus for preparative electrophoresis. The Vortophor consists of three concentric plexiglass cylinders forming two concentri annuli which are vertically oriented.  The outer annulus serves as a jacket through which coolant is passed to remove Joule heat from the inner annulus.  The inner annulus is filled with buffered electrolyte and serves as an electrophoresis chamber.  Electrophoresis is carried out by passing an electric current axially through the inner annulus by means of electrodes located in compartments attached to opposite ends of the central plexiglass cylinder.  Electrical contact is maintained by means of conductive films (e.g., ion exchange or dialysis membranes) which readily pass current but effectively discourage mixing of buffer with the electrode solutions.  Passing a current through the electrolyte in the inner annulus drives the separation of charged solutes, but it also generates Joule heat which can destabilize the chamber hydrodynamics and denature labile biologicals.

Applications and Advantages

■  Can be used for several different types of eletrokinetic separation;  

■  Batch and continuous flow modes of electrophoresis can be performed;

■  Batch isolectic focusing can be performed and extraction at various locations from the processing chamber can be accomplished;

■  System relatively less complex than prior systems;

■  Low cost in both operation and initial construction of the system

■  Provides improved heat transfer and resists problems due to eletro-osmosis while providing good separation of most proteins or other processed chemicals of varying eletrophoretic mobilities.

IP Status 

US Patent No. 5,200,050

Abstract

This invention relates to a rapid and inexpensive method for the preparation of stable, non-denatured, Coomassie Brilliant Blue (CBB) stained proteins that allows efficient association of CBB with a standard protein, such as bovine serum albumin (BSA), without the use of alcohols or acidic solvents. The method forms a dye/protein complex that preserves essential protein nativity. The complex has high spectrophotometric sensitivity and comparatively long chemical stability. The invention also relates to the use of the dye/protein complex in methods for quantitative in vitro detection of tannin analytes.

The method for making the dye/protein complex includes a pulse heating step wherein a protein is heated to a first temperature in a non-alcoholic, aqueous dye solution of CBB for a short pulse period, then cooled to a second temperature to form a mixture containing a dye/protein complex. Optionally, the mixture may be dialyzed against a second non-alcoholic, aqueous solution to exchange solvents and/or remove unbound dye and from the mixture

Excluding dialysis time, the entire method can be performed in less than 10 minutes. The protein in the dye/protein complex is not denatured and, therefore, retains essential native activities. The dye/protein complex is stable and can be stored refrigerated or at room temperature without loss of dye from the complex. The dye/proteins complex is a highly sensitive reagent that is superior to covalently labeled dye/protein complexes prepared with RBB in several properties. In addition, the method is adaptable to the preparation of a variety of dye/protein complexes.

Applications and Advantages

■  Provides a simple, rapid, and economical method to make stable, dye/protein complexes using a sensitive and protein specific dye like CBB under conditions that do not irreversibly denature proteins.

■  Provides a rapid, sensitive, reproducible, and economical way of detecting analytes, like tannins, that bind to dye/protein complexes;

■  Provides an assay method that allows accurate determination of tannin levels present both in a precipitate and supernatant fraction.

IP Status 

US Patent No. 6,057,160

Abstract

The present invention provides an electrophoretic device and method in which a charged solute such as a protein can be simultaneously separated and concentrated by applying a first constant force (e.g., hydrodynamic force due to buffer flow) and opposed by a gradient in a second force (e.g., electric field). According to the invention, a constant hydrodynamic force is opposed by a gradient in the electric field which allows charged molecules to focus in order of their apparent electrophoretic mobilities. The electric field gradient is established and maintained using an array of electrodes whose voltages are individually monitored and adjusted by a computer-controlled circuit board. The computer-generated electric field gradient allows charged molecules to be focused without using a pH gradient. For proteins, because the proteins are not focused at their pls, precipitates do not form, so focused concentrations in excess of 50 mg/mL are not unusual. In addition, because the field shape is dynamically controlled from the computer on a point-by-point basis, the field profile can be adjusted during a run to improve the resolution of components.

Applications and Advantages

■  Provides elecrophoretic methods and devices that that can effectively separate charged solutes, such as protein mixtures, into their component solutes;

■  Batch and continuous flow modes of electrophoresis can be performed;

■  Device offers scale independent control and is modifiable: others parts can be included to detect solute migration;

IP Status 

US Patent No. 6,277,258

Abstract

The challenge of doing dynamic field gradient focusing (DFGF) in the vortex-stabilized electrophoresis apparatus was finding a way to add 32 electrodes to the stator of the apparatus.  Simply adding more electrodes similar to those currently used on the stator was not an option due to the large size of the electrode housings and interference with the fraction collection system.  Additionally, the prospect of maintaining 64 membranes (2 per electrode pair) and seals motivated solution that would also minimize the number of membranes and seals required.  With these thoughts in mind, WSU inventors have developed the following solution:

Placing the electrodes inside the rotor of the vortex-stabilized electrophoresis apparatus eliminates the need for extra seals and membranes as well as avoiding any perturbation of the fraction collection system. 

Also, the engineered vortices that prevent natural convection in the annulus would be unaffected by modifications made inside the rotor.  This solution necessitates some modifications of the current apparatus in order to function.  The inner diameter of the rotor will have to be enlarged to provide space for the electrodes and the cooling buffer.  A vital requirement is that the outside of the rotor needs to be ion permeable, but prevent proteins attracted to the electrodes from leaving the separation chamber.  The apparatus for driving the rotor can remain the same.  Cooling the separation chamber will be performed in a similar fashion. Instead of flowing cooling oil through the hollow of the rotor, a native buffer will be used.  The buffer will then pass through a shell and tube heat exchanger where it will be cooled by chilled silicon oil. 

IP Status 

US and PCT applications pending

Abstract

DC to DC switching power supplies operate by storing energy in inductors, capacitors, or both, then distributing this energy to a load over a time period.  An efficient method used to accomplish this task is to vary the charging time for the energy storage devices depending on the load, for every time period.  This is known as pulse width modulation (PWM) where the charging time per period changes with respect to the load.  Another method is to use pulse code modulation (PCM) where the average value of the control signal keeps the output voltage near the desired level. This invention presents a new digitally programmable structure for the control of DC to DC switching power supplies.  These controllers are stable under DC and low frequency load changes.  The PCM controller eliminates the requirement of existing PWM controllers for matching between the current source and capacitor in the ramp generator.  Both controllers are insensitive to offsets that may exist in design.

Applications and Advantages

■  Provides an improved DC-to-DC switching power supply converter design which provides for the precise, low drift control of output voltage with high efficiency and simplicity of design.

IP Status 

US Patent No. 5,677,618

Abstract

A new way that zone focusing can be conducted with simple buffers in the Vortophor is by introducing or extracting current at a point located between the end electrodes.  This introduces a step change or jump in the electric field which opens a mobility window allowing specific proteins to focus, hence the name ZEFGF.  This technique has the advantage over IEF in that no ampholytes or other potentially expensive buffer modifiers must be added to allow fucusing.  As a result, this technique is relatively inexpensive to apply.

Applications and Advantages

■  Can be used for several different types of eletrokinetic separation;  

■  Batch and continuous flow modes of electrophoresis can be performed;

■  Batch isolectic focusing can be performed and extraction at various locations from the processing chamber can be accomplished;

■  System relatively less complex than prior systems;

■  Low cost in both operation and initial construction of the system

■  Provides improved heat transfer and resists problems due to eletro-osmosis while providing good separation of most proteins or other processed chemicals of varying eletrophoretic mobilities.

IP Status 

US Patent No. 5,298,143

Abstract

Data recently obtained at WSU indicates that a novel enzymatic methods can be used to significantly reduce the cost of Cr (III) analyses and of Cr(VI)/CR(III) speciation.  The method is based on the enzymatic transformation of nitrate to nitrite and observations that metals can selectively inhibit the rate of this transformation.  The activity if enzyme is determined via established techniques that provide a colorimetric determination of the rate of nitrite production. Using these methods, nitrite production, and this enzymatic activity can be determined quickly using a visible light spectrophotmeter or multi-well plate spectrophotometer.  Heavy metal toxicity can be identified by a decrease in the rate of nitrite production when compared to a control that has not been exposed tot eh heavy metal containing sample.  CR (III) inhibits the activity of nitrate reductase over a  concentration range of 1 to 10 mM.  An activity value of 100% indicates the rate of nitrate conversion in the absence of Cr(III). In very lean samples of CR(III), therefore, this technique could be used to directly measure the CR(III) concentration.

Often, however, it is of interest to measure Cr(III) concentrations in the presence of other metals (e.g. CD, Cu, Pb, Zn, and CR(VI)) at similar concentration.  As these metals can also inhibit the nitrate reductase activity such that specifically for Cr(III) analyses, the effects of these metals must be eliminated.  Through the  addition of 1mM nitrillotriacetetic acid (NTA), the inhibitory effects of these metals can be eliminated over typical concentrations of interest.  The addition of NTA removes the inhibitory effects of the other metal ions but does not affect the inhibitory capabilities of Cr(III)  Up to 10 mM NTA does not affect the inhibitory nature of CR(III) of the activity of nitrate reductase.

Further, with NTA eliminating the effects of many common metals, it is often desirable to measure Cr(III) concentrations in the presence of Cr(VI).  1 mM NTA does not eliminate the inhibitory effects of Cr(VI), and that to specifiate between Cr(III) and Cr(VI) further separation will be necessary.  In the hexavalent form, Cr(VI) usually occurs as chromate (CrO) and  dichromate (Cr2)7), with both of these species being divalent anions.  A separation can be effected by the addition of a small amount of anion exchange resin that  will scavenge the anionic Cr(VI) species leaving on the Ct(III) to inhibit the nitrate reductase activity.  This inhibition can be measured either in the lab or the field with a  multi-well plate spectrophotometer.  The multi-well plates could be pre-loaded with the proper amount of reagents including NTA and anion exchange resin to allow rapid analyses of many Cr(III) samples simultaneously (1-386).

Applications and Advantages

This is a novel analytical technique that has application in both the laboratory and in the field as a sensitive and cost effective technique for Cr(III) analyses, replacing the expensive ICP-MS measurements used for most routine applications.  Strong possibility likewise exists to substitute other enzymes for nitrate reductase.

IP Status 

US Patent 6,811,997; 7,169,290

Abstract

Traditionally ion mobility spectrometry (IMS) has been used for the analysis of gas phase compounds, however with the advent of ESI and MALDI the technique's scope of analysis has greatly expanded. The powerful prospects of combining IMS and mass spectrometry (IMMS) to yield instruments capable distinguishing ions based upon both size and mass to charge ratios has led to a large body of work directed at the development of IMMS instruments. While many low pressure (1-100 Torr) IMMS systems have been realized only a limited number of high pressure systems have been developed. Moreover, those which have been described suffer from limitations in the fragmentation information available from such systems.

WSU Researchers have developed an approach to selectively filter and subsequently analyze ion pulses originating from an atmospheric pressure IMS system. These developments enable applications such as IMS-QITMS, IMS-FTMS, IMS-FAIMS and IMS-FAIMS-MS .

Applications and Advantages

■  Many prototype instruments are developed

■  Allows for nD analysis of low abundance species

■  Sensitive

■  Adaptable

IP Status 

US Patent No. 7,560,688

Abstract

The present choice of analytical separation methods that occur under ambient pressure conditions are generally limited to gas chromatography(GC), liquid chromatography (HPLC), capillary zone electrophoresis (CZE) and ion mobility spectrometry (IMS). IMS is about 3 times more efficient than HPLC, 130 times more efficient than GC and almost as efficient as CZE. The utility of these applications largely depends on the size of the equipment. Small high-resolution devices would make these applications more practical and allow for many new applications. While gas IMS methods have shown promising abilities to detect drugs, toxic materials, and explosives, these systems are large and cumbersome due to fundamental limitations of the gas IMS method. Reducing the size of a gas IMS device results in a significant loss in resolution, thus diminishing the utility of small gas IMS devices. Scientists at WSU have developed a liquid phase ion mobility spectrometer (LPIMS) that is capable of overcoming many of the current limitations of traditional gas IMS.

Applications and Advantages

■  Employs a drift liquid

■  Utilizes novel ionization method

■  Separation efficiency two orders of magnitude greater than current methods

■  Greater resolving power over a shorter transit length

■  Enables small high resolution IMS applications

IP Status 

US and PCT application pending

Abstract

Nanostructured separation matrices are formed and may be used to separate molecules.  The devices of the invention can be used to separate molecules including native and detergent-solubilized protein mixtures, protein complexes, nucleic acids (DNA and/or RNA), crystal clusters, nanoparticles, subcellular organelles, viruses, phage, and the like.  The devices can be used in a variety of separation strategies, including isoelectric focusing, isotachophoresis, affinity techniques, gradient techniques, and multidimensional separation strategies based on multidimensional combinations of these techniques.  Significantly, the devices of the invention can be manufactured into networks of nanochannel devices that are integrated with detection systems, thereby permitting evaluation of the purity of bio-molecules at various stages of the purification or analytical procedure and further separation of the biomolecules if desired.

Applications and Advantages

■   Offers efficient separation of proteins in the context of their application to proteomics, environmental science, and advanced diagnostics;

■   Enables high throughput separation, purification, identification, and determination of structure-function relationships of bio-molecular species and biomolecular complexes.

IP Status 

US patent application pending

Abstract

This patented invention is a device that can separate mixtures containing cellular components or those having a large density difference. The device employs a rotating chamber that contains various smaller chambers which aid in the separation. The device is designed to remove the lighter components of the mixture while the device is spinning. The heavy components or cells must be removed once the device has stopped spinning. The device also allows for sampling while separation is occurring - sampling can be performed on the light or heavy fraction as needed. Once the chamber has been cleared, it can be used again.

Applications and Advantages

The CBS system is a continuous plasma separator module, which uses centrifugal force and a patent protected vesicle to achieve plasma separation. It has demonstrated the capability to separate 1-mL of whole blood in less than 30 seconds. The resulting plasma is aspirated on a continuous basis and delivered to the next stage of the analytical process. Clean out is accomplished dynamically. Systems that require greater capacity can achieve higher throughput by joining several CBS modules together.

IP Status 

US patent 6544162 and PCT applications pending

Abstract

Extreme size-focusing of nanoparticles, for instance, enables systemic studies of their physical properties, such as emission, absorption, photoelectric conversion, and photothermal conversion. This WSU invention relates to nanoparticle separation strategies based on pH manipulation in nanofluidic channels by surface charge control and controlled electrolysis. Flow control and focus molecules in nanochannels are shown to be easier with lower electric field and small amount of samples. This separation strategy has wide applications in many areas of science, including photonics, biomedical imaging, etc.

Applications and Advantages

■  Setup versatile enough to separate other charged molecules (e.g. proteins);

■  Requires small amount of sample;

■  Higher sensitivity and greater reproducibility;

IP Status 

US patent application(s) pending

Abstract

This WSU invention relates to the methods and devices that enhance the time-domain signal of a Fourier-transform ion-cyclotron resonance mass spectrometer (FTICR-MS) and provide enhanced resolution and accuracy of mass measurements. FTICR-MS is an important analytical tool for ion analysis, especially in analyzing complex mixtures. Specifically, this invention relates to ion cyclotron resonance (ICR) cells and other ion-trapping cells with plural groups of multiple trapping electrodes for shaping (e.g., flattening) the radial electric field within the ICR cell. It also relates to methods for controlling the electric field to diminish effects of de-phasing. The diminished effects are achieved by decreasing space-charge contributions by increasing the length of the ion-oscillation path along the z-axis of the ICR cell.

Applications and Advantages

This invention enhances performance of FTICR mass spectrometry systems through the minimization of effects that lead to ion collisions and ion de-phasing.

IP Status

US patent issued                                         

Publication

Kaiser, Nathan and Bruce, James. Reduction of Ion Magnetron Motion and Space Charge using Radial Electric Field Modulation. International Journal of Mass Spectrophotometry 265, 2007. 271-280.

Abstract

The ability to identify and quantitate the relative abundance of f-block elements present in environmental and industrial samples is of critical importance to national security. Current methods are slow, labor intensive and cannot be easily integrated into industrial systems. As reprocessing technologies become common within the nuclear industry the ability to accurately inventory materials on site in real time represents a key enabling technology for safe and secure operations. With over 400 nuclear power plants in operation, another 60 under construction and 500 in planning worldwide there is a clear need for agile technologies that provide a facile means for material inventory. WSU scientists have developed a low-cost, portable instrumentation and methods for rapid separation and quantitation of f-block elements to meet this need.

Applications and Advantages

This WSU invention is simple, quicker than existing techniques, and mercury-free procedure for pre-concentrating trace level trivalent f-elements from bulk aqueous solution that allows for follow on separation and detection.

IP Status

US patent application

Abstract

This WSU invention provides a novel approach for in-situ remediation of chemically contaminated soils using shock waves or large amplitude stress waves. Shock waves have the following features: a) large compression, b) large increase in temperature, c) non-hydrostatic or shear deformation, and d) short time scales. More specifically, shock waves, of an amplitude and duration sufficient to effectively induce decomposition and/or polymerization of organic chemical dispersed in geologic media, are administered to a soil site to reduce the levels of harmful chemicals.

Applications and Advantages

■   Provides a rapid and cost-effective remediation method of in-situ treatment of contaminated soils

IP Status 

US Patent No. 6,204,429

Abstract

Ion mobility spectrometry (IMS), a powerful tool commonly used for security applications (e.g. search for explosives, narcotics, and other trace contrabands) does not achieve optimal separation power with both small and large ions simultaneously present. Similar to the general elution problem of chromatographic experiments, small ions are well resolved using a low electric field, whereas large molecules are best separated using a higher electric field. While using a low electric field, IMS systems tend to suffer from low ion transmission and low signal-to-noise ratios.

WSU scientists have alleviated these effects using a software-created second gate and a novel voltage algorithm. The electric field was swept from low to high while monitoring a specific drift time using the second gate creating a ‘voltage-sweep’ spectrum. This spectrum suffers from similar drawbacks to a standard, drift-time experiment: the selection of a fast drift time will resolve peaks with a low mobility and a slow drift time will resolve peaks with high mobilities, while sacrificing signal-to-noise. However, if an optimal drift time is calculated for each voltage and scanned simultaneously, a spectrum may be obtained with optimal separation throughout the range. This increases the resolving power of each peak in the spectrum and allows simultaneous separation of peaks for both low and high mobility compounds. In addition, it permits the accurate measurement of mobilities by measuring the drift times in an electric field continuum. Most importantly, this technique extends the peak capacity of any IMS system and, since the voltage algorithm requires only minimal changes to the existing software, it may be applied to any IMS system wherein the voltage may be dynamically changed.

Applications and Advantages

■  Improves analysis time and resolving power resulting to increased information from a stand-alone IMS system

IP Status

US patent application

Abstract

The availability of small, low-power devices, which filter, amplify and transmit weak electrophysiological signals, has traditionally been a bottleneck in the development of subject monitoring equipment. Current state of the art equipment utilizes relatively few electrodes operating over a relatively narrow frequency range at relatively low speed. Due in part to the limited availability of high performance devices, data outside the frequency and intensity regime provided by current instrumentation has been sparse. This has led to a false impression that data outside of the parameters is of little importance, which in turn has led to a slow to develop demand for such high performance devices.

Recent studies exploiting custom built high performance instrumentation have demonstrated the need for such high performance devices. While this is becoming apparent to those within the industry, there is presently a race to develop devices with increased capabilities. At present, a WSU team has a device that vastly out-performs the current state of the art.

WSU researchers have developed a small, highly sensitive, low-cost system capable of processing, correlating and wirelessly transmitting data from events occurring at frequencies ranging from DC to 7kHz. The signal processing component is contained on a single chip, which can independently process 16 channels of information. Moreover, custom designed software and hardware with the capability to control individual channels in real time, correlate the signals in time to a video feed and communicate with multiple signal processing chips. The current prototype of the device is operable for the measurement of EEG (electroencephalography) in laboratory mice. System attributes include: DC coupled, high sensitivity (1mv), 110 dB dynamic range, 24 bit ADC sampling 16-256 channels @ 32kHz and optimized for minimal power consumption.

Applications and Advantages

■  Lightweight

■  Wide frequency range

■  DC coupled- allows for errors in positioning and enables processing of DC signals

■  High sensitivity and dynamic range

IP Status 

US and PCT applications pending

Abstract

Bronchoscopy allows for the evaluation of the trachea (windpipe), carina (sensitive area within the trachea), and bronchi of an animal patient.  General anesthesia is required for bronchoscopy to suppress coughing and laryngospasm and to allow for examination of the airway without inducing trauma.

To perform a veterinary bronchoscopy, the standard procedure is to disconnect the anesthetized patient from oxygen and anesthesia and insert a flexible endoscope down the airway for evaluation purposes.  Once the patient’s blood oxygen saturation falls below 80%, the endoscope must be removed and the oxygen/anesthesia reconnected to the patient.  Once the patient’s blood oxygen saturation levels have recovered, the whole process of disconnecting the oxygen/anesthesia and reinserting the endoscope begins again.  This process continues until the exam is completed.

One alternative is to supply oxygen to the patient through the endoscope’s biopsy channel, if the endoscope is so equipped.  This will extend the examination time from seconds to minutes.  However, using this approach can result in excessive oxygen flow to the patient, which can result in rupture of alveoli or even pneumothorax (collapsed lung).  The BGTG is a novel device that allows a complete exam while maintaining proper blood oxygen saturation levels without having to remove the endoscope and interrupt the exam.  Examination times are significantly reduced using the BGTG device.

Applications and Advantages

This low cost-device allows bronschocopy while administering oxygen/anesthesia and maintaining oxygen saturation throughout the procedure.

IP Status

US Patent Application No. 61/271,684

Abstract

Inserting feeding tubes into animal patients during esophagostomy procedures (insertion through the neck to the esophagus) can be difficult.  Scarring and other tissue damage can occur if the procedure is done incorrectly.  A special feeding tube insertion device developed at WSU can be used to simplify the procedure making it safer and quicker to accomplish with minimal discomfort to the animal.

Applications and Advantages

■  Decreases risk to animals during surgery

■  Reduce time of procedure to 5 minutes

■  Saves money (use of anaethesia and personnel)

■  Easy to use

IP Status

US Patent No. 61/292,960

Abstract

When a colonoscopy is preformed on a subject the colon is first insufflated with a gas to expand the internal chamber.  Often, air escapes through the anal sphincter, thus, requiring a manual compression of the sphincter for the duration of the examination.  WSU inventors have developed a gas-tight endoscope guide -- a plastic device for guiding the endoscope and creating a gas-tight barrier between the animal patient and the operator during colonoscopy procedures.  The gas-tight guide prevents the passage of gases, secretions, and fluids during the procedure thus reducing the risk of complications.

Applications and Advantages

This low cost-device allows bronschocopy while administering oxygen/anesthesia and maintaining oxygen saturation throughout the procedure.

IP Status

US Patent No. 61/271,706

Abstract