Scripps scientists lead two projects to track potentially toxic chemicals in marine life, impacts on human health.

(From left) Paul Jensen, Brad Moore, Eric Allen, Lihini Aluwihare of Scripps and Eunha Hoh of San Diego State University.

Capitalizing on UC San Diego’s unique ability to address environmental threats to public health, a new center based at Scripps Institution of Oceanography at UC San Diego will target emerging contaminants found naturally in common seafood dishes as well as man-made chemicals that accumulate in human breast milk.

With $6 million in joint funding from the National Institutes of Health and the National Science Foundation, the new Scripps Center for Oceans and Human Health will track natural chemicals known as halogenated organic compounds, or HOCs. Human-manufactured varieties include polybrominated diphenyl ethers, or PBDEs, chemicals that until recently were manufactured and broadly used in commercial products as flame retardants in the textile and electronics sectors.

Less is known about the natural versions of HOCs that accumulate in marine mammals such as seals and dolphins and have been identified in top predators that humans consume such as tuna and swordfish. While PBDEs are well known for their toxicity and have been linked to a variety of human diseases, including cancer and thyroid ailments, the origin and transmission of their natural counterparts are poorly understood.

The Scripps Center for Oceans and Human Health will investigate the biology and chemistry behind these natural contaminants in the Southern California Bight, from Point Conception in Santa Barbara south to Ensenada, Mexico.

“The new Center for Oceans and Human Health is uniting leading experts in oceanography and medicine, two areas that make UC San Diego one of the best and most unique universities in the world, to address an emerging threat to public health and safety,” said UC San Diego Chancellor Pradeep K. Khosla. “UC San Diego is proud to be leading this effort in collaboration with other prominent institutions around the San Diego region.”

“The Scripps Center for Oceans and Human Health is focused on addressing to what extent nature contributes to the production and transmission of these toxins in the marine environment,” said Bradley Moore, director of the new center and a professor of oceanography and pharmaceutical sciences at Scripps and the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. “Southern California waters will be the focus of our study, in part because our state has the highest reported incidence of polybrominated chemicals in human breast milk in the world.”

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UCLA study shows versatility of nanodiamond as targeted drug-delivery agent to tumor site.

Nanodiamonds bound to the chemotherapy drug epirubicin are enclosed within a lipid membrane and coupled to antibodies specific to hard-to-treat tumors. These hybrid drug delivery agents cause tumors to regress in size while markedly improving drug tolerance.

Recently, doctors have begun to categorize breast cancers into four main groups according to the genetic makeup of the cancer cells. Which category a cancer falls into generally determines the best method of treatment.

But cancers in one of the four groups — called “basal-like” or “triple-negative” breast cancer (TNBC) — have been particularly tricky to treat because they usually don’t respond to the “receptor-targeted” treatments that are often effective in treating other types of breast cancer. TNBC tends to be more aggressive than the other types and more likely to recur, and can also have a higher mortality rate.

Fortunately, better drug therapies may be on the horizon. UCLA researchers and collaborators led by Dean Ho, a professor at the UCLA School of Dentistry and co-director of the school’s Jane and Jerry Weintraub Center for Reconstructive Biotechnology, have developed a potentially more effective treatment for TNBC that uses nanoscale, diamond-like particles called nanodiamonds.

Nanodiamonds are between 4 and 6 nanometers in diameter and are shaped like tiny soccer balls. Byproducts of conventional mining and refining operations, the particles can form clusters following drug binding and have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs’ desired effect. In the UCLA study, the nanodiamond delivery system has been able to home in on tumor masses in mice with triple negative breast cancer.

Findings from the study are published online today (April 15) in the peer-reviewed journal Advanced Materials.

“This study demonstrates the versatility of the nanodiamond as a targeted drug-delivery agent to a tumor site,” said Ho, who is also a member of the California NanoSystems Institute at UCLA, UCLA’s Jonsson Comprehensive Cancer Center and the UCLA Department of Bioengineering. “The agent we’ve developed reduces the toxic side effects that are associated with treatment and mediates significant reductions in tumor size.”

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Recon 2 is most comprehensive virtual reconstruction of human metabolic network to date.

Researchers liken Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map.

Building on earlier pioneering work by researchers at the University of California, San Diego, an international consortium of university researchers has produced the most comprehensive virtual reconstruction of human metabolism to date. Scientists could use the model, known as Recon 2, to identify causes of and new treatments for diseases like cancer, diabetes and even psychiatric and neurodegenerative disorders. Each person’s metabolism, which represents the conversion of food sources into energy and the assembly of molecules, is determined by genetics, environment and nutrition.

The researchers presented Recon 2 in a paper published online March 3 in the journal Nature Biotechnology.

Doctors have long recognized the importance of metabolic imbalances as an underlying cause of disease, but scientists have been ramping up their research on the connection as a result of compelling evidence enabled by the Human Genome Project and advances in systems biology, which leverages the power of high-powered computing to build vast interactive databases of biological information.

“Recon 2 allows biomedical researchers to study the human metabolic network with more precision than was ever previously possible. This is essential to understanding where and how specific metabolic pathways go off track to create disease,” said Bernhard Palsson, Galletti Professor of Bioengineering at UC San Diego Jacobs School of Engineering.

“It’s like having the coordinates of all the cars in town, but no street map. Without this tool, we don’t know why people are moving the way they are,” said Palsson.

He likened Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map. For example, researchers looking at how metabolism sets the stage for cancerous tumor growth could zoom in on the “map” for finely detailed images of individual metabolic reactions or zoom out to look at patterns and relationships among pathways or different sectors of metabolism. This is not unlike how you can get a street view of a single house or zoom out to see how the house fits into the whole neighborhood, city, state, country and globe.  And just as Google maps brings together a broad set of data – such as images, addresses, streets and traffic flow – into an easily navigated tool, Recon 2 pulls together a vast compendium of data from published literature and existing models of metabolic processes.

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“This is going to remove a major bottleneck in the field.”

The bacterial enzyme Cas9 is the engine of RNA-programmed genome engineering in human cells.

A simple, precise and inexpensive method for cutting DNA to insert genes into human cells could transform genetic medicine, making routine what now are expensive, complicated and rare procedures for replacing defective genes in order to fix genetic disease or even cure AIDS.

Discovered last year by Jennifer Doudna and Martin Jinek of the Howard Hughes Medical Institute and University of California, Berkeley, and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine-Sweden, the technique was labeled a “tour de force” in a 2012 review in the journal Nature Biotechnology.

That review was based solely on the team’s June 28 Science paper, in which the researchers described a new method of precisely targeting and cutting DNA in bacteria.

Two new papers published last week in the journal Science Express demonstrate that the technique also works in human cells. A paper by Doudna and her team reporting similarly successful results in human cells has been accepted for publication by the new open-access journal eLife.

“The ability to modify specific elements of an organism’s genes has been essential to advance our understanding of biology, including human health,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute Investigator at UC Berkeley. “However, the techniques for making these modifications in animals and humans have been a huge bottleneck in both research and the development of human therapeutics.

“This is going to remove a major bottleneck in the field, because it means that essentially anybody can use this kind of genome editing or reprogramming to introduce genetic changes into mammalian or, quite likely, other eukaryotic systems.”

“I think this is going to be a real hit,” said George Church, professor of genetics at Harvard Medical School and principal author of one of the Science Express papers. “There are going to be a lot of people practicing this method because it is easier and about 100 times more compact than other techniques.”

“Based on the feedback we’ve received, it’s possible that this technique will completely revolutionize genome engineering in animals and plants,” said Doudna, who also holds an appointment at Lawrence Berkeley National Laboratory. “It’s easy to program and could potentially be as powerful as the Polymerase Chain Reaction (PCR).”

The latter technique made it easy to generate millions of copies of small pieces of DNA and permanently altered biological research and medical genetics.

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Method could be used to make novel designer drugs that can’t be produced in other systems.

Biologists at UC San Diego have succeeded in genetically engineering algae to produce a complex and expensive human therapeutic drug used to treat cancer.

Their achievement, detailed in a paper in this week’s early online issue of The Proceedings of the National Academy of Sciences, opens the door for making these and other “designer” proteins in larger quantities and much more cheaply than can now be made from mammalian cells.

“Because we can make the exact same drug in algae, we have the opportunity to drive the price down dramatically,” said Stephen Mayfield, a professor of biology at UC San Diego and director of the San Diego Center for Algae Biotechnology or SD-CAB, a consortium of research institutions that is also working to develop new biofuels from algae.

Their method could even be used to make novel complex designer drugs that can’t be produced in any other systems — drugs that could be used to treat cancer or other human diseases in new ways.

“You can’t make these drugs in bacteria, because bacteria are incapable of folding these proteins into these complex, three-dimensional shapes,” said Mayfield. “And you can’t make these proteins in mammalian cells because the toxin would kill them.”

The advance is the culmination of seven years of work in Mayfield’s laboratory to demonstrate that Chlamydomonas reinhardtii, a green alga used widely in biology laboratories as a genetic model organism can produce a wide range of human therapeutic proteins in greater quantity and more cheaply than bacteria or mammalian cells.

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“What’s Past is Prologue: Creating the Life Science Industry in San Diego” on Nov. 7.

Three legendary San Diego venture capitalists will discuss past lessons learned and thoughts about the future of local commercial biotech ventures during the first in a series of planned “conversations” Nov. 7 in Calit2’s Atkinson Hall at UC San Diego. The event is being billed as the first of its kind in San Diego.

“What’s Past is Prologue:  Creating the Life Sciences Industry in San Diego” is sponsored by the Life Sciences Foundation and the UC San Diego Library, and co-sponsored by CONNECT, BioMed Realty, Enterprise Partners Venture Capital, and Sughrue Mion, with community partners BIOCOM and San Diego Venture Group. The panelists, who will offer their insights into the past and future of San Diego biotech, will include Jim Blair of Domain Associates, Kevin Kinsella of Avalon Ventures, and Tim Wollaeger of Sanderling Partners. Ivor Royston of Forward Ventures will serve as moderator. The 4 p.m. discussion will be followed by a reception at 5 p.m.

Blair, Kinsella and Wollaeger helped to create the San Diego life sciences industry more than 30 years ago, and remain active today. Creating such high profile companies as Dura Pharmaceuticals, Vertex and Pyxis, they will discuss the birth of San Diego’s life sciences cluster, current conditions, and their vision for the future.

Moderator Ivor Royston, M.D., is a founding managing partner of Forward Ventures. Royston has been involved in the biotechnology industry in San Diego from its inception in 1978 with the founding of Hybritech Inc., later acquired by Eli Lilly, and with the founding of Idec Pharmaceuticals in 1986, which later merged with Biogen.

Tickets for the Nov. 7 event are $25. For more information and to register, please visit: lifesciencesfoundation.org/sandiego.

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UC’s QB3 has helped launch 60 companies.

Universities not only provide the ideal petri dish for cultivating bioscience with commercial potential, but have a moral obligation to do so, given the opportunity to translate public funding into health and jobs, according to a new case study by UCSF researchers.

In an analysis published Wednesday in Science Translational Medicine, researchers at the California Institute for Quantitative Biosciences (QB3) assessed the impact of the institute’s efforts over the past eight years in supporting entrepreneurs on the three UC campuses in which it operates: UC San Francisco, UC Berkeley and UC Santa Cruz.

The study found that, by lowering the hurdle even very slightly for scientists to become entrepreneurs, the scientists were able to gain extraordinary traction in translating academic research into public benefit, generating 60 new companies in the first six years and attracting 75 new bioscience entrepreneurs in the last year alone.

“This fundamentally changes the way we think of academic science,” said Douglas Crawford, Ph.D., assistant director of QB3 and senior author on the paper. “There is a distressing paucity of new drugs in the pipeline and a clear need for new economic engines in this country. This is a call to action to address that.”

The paper cites the following essential support that universities can provide:

• Bioscience-focused incubators
• An open network approach that enables any entrepreneur to participate
• Competitive seed funding options
• Real-world mentoring that gives scientist a clear sense of market needs.

In the first six years since QB3 started supporting entrepreneurs at the UCSF Mission Bay campus, its growing network of incubators helped launch 60 new bioscience companies at UCSF and across the San Francisco Bay at UC Berkeley — at a cost of $1 million per year. Of those, 56 are still in business, and 13 have moved beyond the incubator network or have been purchased by larger companies.

Together, those companies have created more than 280 jobs and attracted more than $230 million in either small business grants or venture capital funding for those companies, which are primarily focused on developing therapeutics, medical devices and research tools. That’s a 38-fold return on investment, despite current negative trends in seed-stage investing, in addition to the public benefit of any products those companies generate.

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Five3 Genomics offers genomics software and services for personalized cancer therapy.

The co-founders of Five3 Genomics are (from left) Charles Vaske, Steven Benz, and Zachary Sanborn, all former graduate students in the UC Santa Cruz Baskin School of Engineering.

The co-founders of Five3 Genomics, a new biotech company based in Santa Cruz, are former graduate students in the Baskin School of Engineering at UC Santa Cruz, where they helped develop innovative cancer genomics software.

Their company, which has signed a license agreement with UCSC, offers software and services for cancer researchers, pharmaceutical companies, and health care organizations. Its goal is to provide the data processing and analysis required for personalized cancer therapy, in which treatments are matched to the specific genetic aberrations found in an individual patient’s cancer cells.

“We’re working with academic collaborators to build out the platform and starting conversations with pharmaceutical companies and insurance companies,” said CEO Steve Benz, who completed his Ph.D. in bioinformatics this year. “It’s a great opportunity to be able to take this technology and commercialize it so that it can be used to help patients.”

In addition to Benz, the co-founders of Five3 Genomics include Chief Technical Officer Zachary Sanborn and Chief Scientific Officer Charles Vaske. All three of them worked as graduate students with UC Santa Cruz bioinformatics experts David Haussler and Joshua Stuart, who are doing pioneering work in the field of cancer genomics. Haussler, a professor of biomolecular engineering and Howard Hughes Medical Institute investigator, said that Benz, Sanborn, and Vaske were “brilliant grad students.”

“Working at UCSC they were exposed to the cutting edge in computational genomics,” Haussler said. “They played a key role in developing our cancer genomics program. They are pure self-starters, and developed the code to implement their ideas from the bottom up. The algorithms they developed represented new breakthroughs in our ability to interpret DNA sequence information obtained from cancer tumors. This area is poised to move from the academic realm into the clinical realm in the next few years. By spinning off a startup company, they have put themselves in an excellent position to play a key role in this transformation.”

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UC BRAID is helping to reduce barriers to biomedical research.

UC BRAID program leaders (from left) Gary Firestein (UC San Diego), Dan Cooper (UC Irvine), Lars Berglund (UC Davis), Clay Johnston (UCSF) and Steven Dubinett (UCLA)

With a focus on improving biomedical research collaboration within the University of California system, representatives from five UC campuses and the UC Office of the President (UCOP) met recently for an annual retreat in Oakland to review the progress of the University of California Biomedical Research Acceleration, Integration, and Development (UC BRAID) program.

Since 2010, the UC BRAID consortium has been working to bring together UC’s five health campuses — Davis, Irvine, Los Angeles, San Diego and San Francisco — with the goal of reducing barriers to biomedical research by pooling data, resources and expertise.

“After only two years, we are seeing real success,” said UC BRAID Chair Clay Johnston, M.D., Ph.D., associate vice chancellor of research at UCSF and director of the Clinical and Translational Science Institute (CTSI). “Thanks in large part to support from UCOP, which provides critical funding and in-kind support, this group has become a center of coordination and cross-campus synergy that is having a demonstrably positive effect on research at UC.”

Participants at the Sept. 14 event, including UCOP’s Steven Beckwith, Ph.D., vice president for research and graduate studies, and John Stobo, M.D., senior vice president for health sciences and services, discussed how UC BRAID has created a uniquely powerful virtual biomedical research institution.

Among UC BRAID’s early successes is the creation of the UC Research Exchange (UC ReX), an unprecedented cross-campus searchable database of patient-level study data from all UC medical centers. UC ReX enables physicians and scientists to identify and recruit patients from across the five health campuses based on diagnosis and demographics, with more characteristics to be added soon.

“UC ReX is a unique resource that will expand our clinical trial networks, enhance outcomes research, and facilitate quality-of-care studies,” said UC BRAID Vice Chair Gary Firestein, M.D., dean and associate vice chancellor of translational medicine and director of the Clinical and Translational Research Institute at UC San Diego. “These efforts, particularly UC ReX, demonstrate how much five institutions with aligned goals can accomplish in a short period of time,” he said.

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UCSF part of industry contributing $16.7B a year to economy.

UCSF and its affiliates have been successful in the transformation of San Francisco as a leading center of innovation in health care and biosciences, according to a new report released Wednesday.

The combined economic impact of hospitals, biomedical research and health sciences education generates $16.7 billion and more than 100,000 jobs per year — almost one in five jobs in the city and county of San Francisco, according to the report by economist Philip King, Ph.D., an assistant professor at San Francisco State University.

“The San Francisco Bay Area is known as a center of innovation,” King says. “Less reported is the role of health and medical technology on the Bay Area’s economy, in particular, San Francisco’s economy. Much attention has been focused on social media companies like Twitter and Zynga. But another significant revolution is under way in San Francisco — in biomedical research and technology.”

King emphasized these points in a report released Wednesday at ForecastSF, the region’s leading economic and jobs summit presented by the San Francisco Chamber of Commerce, Wells Fargo and the San Francisco Center for Economic Development.

The report, commissioned by the Hospital Council of Northern and Central California, the Chamber of Commerce, UCSF and others, follows up on last year’s analysis of hospitals and expands the focus to examine San Francisco’s role as a leading center in health care, education and bioscience research.

San Francisco Mayor Ed Lee referred to the economic power of the life sciences sector as the “silent giant,” when compared to the much-touted high-tech sector. Lee said that he will meet quarterly with the Hospital Council to ensure that the city drives economic growth and supports innovation in health care and research discovery aimed at solving diseases such as cancer and Alzheimer’s.

UCSF Chancellor Susan Desmond-Hellmann, M.D., M.P.H., described what she calls the secret sauce of innovation in San Francisco in a video that premiered at the ForecastSF summit. “It’s complicated,” she said, “but there are some important elements: a strong commitment to world-class care for all of our residents; 14 hospitals dedicated to improving the health of our community; 108 bioscience companies which either started here or decided to relocate here; and very importantly, we have great universities, colleges and research institutes that are conducting groundbreaking research, and training the next generation of scientists, health care professionals and technicians.”

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TeselaGen’s DNA construction technology makes genetic engineering cheaper and faster.

TeselaGen co-founders (from left) Eduardo Abeliuk, Mike Fero and Nathan Hillson have licensed technology from JBEI.

Sequencing, splicing and expressing DNA may seem to be the quintessence of cutting-edge science—indeed DNA manipulation has revolutionized fields such as biofuels, chemicals and medicine. But in fact, the actual process can still be tedious and labor-intensive, something Lawrence Berkeley National Laboratory (Berkeley Lab) scientist Nathan Hillson learned the hard way.

After struggling for two days to design a protocol to put together a genetic circuit with 10 pieces of DNA—using a spreadsheet as his primary tool—he was dismayed to discover that an outside company could have done the whole thing, including parts and labor, for lower cost than him ordering the oligonucleotides himself. “I learned two things: one, I never wanted to go through that process again, and two, it’s extremely important to do the cost-effectiveness calculation,” said Hillson, a biochemist who also directs the synthetic biology program at the Berkeley Lab-led Joint BioEnergy Institute (JBEI). “So that was the genesis of the j5 software. This is the perfect thing to teach a computer to do.”

The j5 software package, which has attracted users from more than 250 institutions worldwide since it was made available last year, is now the basis for the latest startup to emerge from JBEI, a Department of Energy research center established in 2007 to pursue breakthroughs in the production of cellulosic biofuels. By building on j5 and adding modules for commercial users, TeselaGen Biotechnology, founded by Hillson and two partners, says it will significantly reduce the time and cost involved with DNA synthesis and cloning, a multibillion-dollar market.

“It’s like AutoCAD for biology,” said TeselaGen co-founder and CEO Mike Fero. “Modern cloning is a computational problem. We are the missing informatic piece to making modern scarless DNA assembly methods a reality for the majority of biologists. Otherwise it’s a small cadre of people who can do it.”

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UC Davis engineering incubator aims to speed innovative ideas to the marketplace.

Nano-Sharp co-founder Saif Islam, a UC Davis engineering professor, loads a silicon wafer into a machine that etches razor patterns.

A new startup company at UC Davis aims to bring you a better shave through semiconductor manufacturing technology. Nano-Sharp Inc. plans to use silicon wafers to make razor blades and surgical tools far more cheaply than current silicon or ceramic blades.

It’s one of three new companies in the College of Engineering’s incubator, the Engineering Translational Technology Center. The new businesses hope to grow into viable companies that attract private funding.

“Every single one of these companies is looking at a multibillion dollar market,” said Jim Olson, the center’s business specialist and a visiting assistant professor at the UC Davis Graduate School of Management.

Nano-Sharp co-founder Saif Islam, professor of electrical and computer engineering, said that inspiration came when his team was working on making solar cells from silicon wafers. They were etching the wafers to create thin vertical walls standing up from the surface.

“We accidentally made some ‘bad’ walls that were very sharp,” he said. “We realized that we could mount them and use them as blades.”

Ceramic or silicon blades are extremely sharp and keep an edge much longer than metal blades. But they are very expensive, so their use is limited to high-end kitchen knives and surgical tools. For example, a ceramic scalpel for eye surgery costs about $600, Islam said.

Conventional blades are made by sharpening the edge of a silicon wafer, Islam said. In contrast, his new, patented technique creates blades across the surface of the wafer.

The cutting edge of the blade is just a few atoms across, Islam said. “They have atomic sharpness approaching that of a diamond blade that metal blades cannot exhibit.”

The performance of these crystalline blades can be improved using technologies developed by the semiconductor industry over the last 50 years, Islam said.

Islam recently won a Proof of Concept award from the University of California to develop a prototype to attract private investors to back the company.

Co-founders of the company are Logeeswaran V. Jayaraman, postdoctoral researcher in Islam’s laboratory, and David Horsley, professor of mechanical and aerospace engineering.

Other new tenants

Other new tenants in the incubator are mRhythm and Barobo Inc. Founded by professor Tingrui Pan of the Department of Biomedical Engineering, mRhythm is developing sensors for personal home health monitoring. The small, flexible sensors can be worn by patients at home to record data such as heart rate, breath sounds and patterns, transmitting the information wirelessly to health care professionals.

Educational robotics company Barobo, founded by professor Harry Cheng of the Department of Mechanical and Aerospace Engineering and former graduate student Graham Ryland, has its physical office at the Davis Roots incubator in the city of Davis. It is working with ETTC for advice on business development and fundraising.

Continuing tenants

Ennetix Inc. (formerly PutahGreen Systems) is focused on dramatically reducing the energy consumed by IT networks and connected systems across the world. The company was founded on research by Biswanath Mukherjee, distinguished professor of computer science, and licensed exclusively to Ennetix. The company recently hired Jonathan Symons as its chief executive officer and closed its first round of angel funding.

Inserogen is a biotech startup based on using tobacco plants as “biofactories” for high-value recombinant proteins, life-saving therapeutics and vaccines. The technology is quick, scalable and cost effective. Inserogen was the first prize winner of the 2010 Big Bang! Business Plan Competition at UC Davis. Founders Lucas Arzola and Professor Karen McDonald have won grants from the National Collegiate Inventors and Innovators Alliance (NCIIA) and the National Science Foundation Innovation Corps program, allowing them to develop a proof of concept and to explore the commercialization potential of this proprietary technology.

ETTC was established in 2010 to help technology startups, based on intellectual property developed at UC Davis, grow and attract support from external financial investors. The center provides companies with space close to the college’s laboratories as well as support, mentorship and introductions to potential investors and strategic partners. Members are selected for admission into the business incubator through a review process that includes an assessment of the commercial potential of the faculty research and its readiness for commercial development.