TAG: "biomedicine"

Big data in biosciences, health care is focus of new UCLA research center


Institute for Quantitative and Computational Biosciences will advance biomedical sciences.

Alexander Hoffmann and his colleagues will collaborate with mathematicians to make sense of a tsunami of biological data. (Photo by Reed Hutchinson, UCLA)

By Stuart Wolpert, UCLA

A new research institute at UCLA may eventually provide doctors with tools to more accurately tailor medicines for individual patients, which could both improve quality of care and minimize the side effects associated with today’s medicine.

The Institute for Quantitative and Computational Biosciences will employ multidisciplinary research to study how molecules and genes interact. Its goal: unlocking the biological basis of health and disease by tapping the power of big data and computational modeling.

“UCLA’s Institute for Quantitative and Computational Biosciences will have a major, positive impact on human health,” said UCLA Chancellor Gene Block. “It will engage exceptional faculty from the life sciences and physical sciences, and our David Geffen School of Medicine and Henry Samueli School of Engineering and Applied Science to ensure that UCLA is at the forefront of research that will help usher in a new era of personalized health care, and to transform research and education in the biosciences.”

The institute is led by Alexander Hoffmann, professor of microbiology, immunology and molecular genetics in the UCLA College, whose research aims to understand how our genes interact to ensure health or produce disease — and the roles played by such factors as food, environmental stresses, infectious agents and pharmaceuticals. Among the diseases for which Hoffmann’s research may lead to significant progress are cancer and immune disorders, because they are caused by errors in cellular decision-making.

Hoffmann says that biology’s million-dollar question is how genes and environment interact to ensure health or cause disease, he said. As UCLA researchers work to answer that question, they will collaborate with UCLA mathematicians who will create mathematical models that help them make sense of a tsunami of biological data.

“Biology is entering a new phase,” Hoffmann said. “So far, biology has been much less math-based than the other sciences. Since the sequencing of the human genome in the early 2000s, there has been an irreversible change in the way biology and biomedical research are being done. At UCLA, we will lead research in that direction and connect basic and applied sciences in an unprecedentedly productive collaboration.”

Victoria Sork, dean of the UCLA Division of Life Sciences, said the institute’s approach represents the “new life sciences” and predicts that the new center will accelerate discovery and translational application in many areas, including medicine, the environment, energy, and food production and food safety.

“Technological breakthroughs are enabling scientists to analyze not only one gene at a time, but how hundreds or thousands of genes work together,” Sork said. “Combined with big data, new knowledge of critical gene networks will lead us to a better understanding of what makes humans healthy.”

The road to “precision medicine”

Dr. A. Eugene Washington, vice chancellor of UCLA Health Sciences and dean of the David Geffen School of Medicine at UCLA, said the new era of personalized medicine will offer higher-quality health care — and possibly lower-cost care — because genetic information will give health providers better knowledge about individual patients.

“We are likely to see significant change in health care in the coming years as genetic data for individuals become more widely available,” Washington said.

In fact, big data already has begun to transform health care. In the past, doctors treating people with a certain disease might have relied solely on their own or their colleagues’ experience treating others with the same disease. Now, instead of relying on a small number of case studies, physicians can turn to mountains of data to guide their approach.

“We haven’t yet begun to fully tap into the knowledge we have about how we have treated millions of patients,” said Dr. Steven Dubinett, director of the UCLA Clinical and Translational Science Institute, and UCLA’s senior associate dean for translational research and associate vice chancellor for research.

“Now, with the rise of big data, we have the capability to utilize a network of brains in a highly sophisticated manner so that all our experience at UCLA, in the University of California system and the many other hospitals with which we share data can be brought to bear on patient treatment in a way that was not possible before.”

The result may be not only personalized health care, but “precision medicine”—the ability for doctors to accurately predict positive health outcomes for patients, Dubinett said.

The move to big data also is dramatically changing the skill sets required for life sciences and biomedical researchers: Increasingly, backgrounds in mathematics, computer science and physics will be highly sought after. Already, UCLA is planning new programs through which computational scientists will train clinicians so they can understand how to work with large sets of data and apply the insights they gain to treating patients.

In addition, UCLA has established a doctoral program in bioinformatics, and the Clinical and Translational Science Institute, in which UCLA is one of four partner institutions, is at the forefront of utilizing big data in clinical care — including developing new pharmaceuticals and bringing important new discoveries into the community.

Much of the data UCLA faculty will work with will come from the University of California Research eXchange, which manages an extremely large repository of clinical data — more than 12 million patient records. Dubinett said UCReX is in the process of adding millions of additional records through partnerships with other Los Angeles medical institutions and, eventually, other academic medical centers in California and throughout the U.S. (Patients’ identities are not released to researchers.)

Dubinett said UCLA will be a national leader in this revolution in personalized health care, in part because UCLA’s medical center is part of its main campus — something that is not the case at many other research universities. That close proximity makes it easier for doctors to collaborate with experts in biomedical informatics and other fields, and has been a lure for many of the exceptional scientists joining the effort.

To strengthen the new institute, UCLA has hired nine faculty members since July 2011 and has plans to hire additional faculty in the next several years. One of the new hires was Leonid Kruglyak, who came to UCLA from Princeton University in 2013. Kruglyak uses big data in his genetics research and, according to Sork, is a “brilliant superstar of the highest stature.”

Among the other outstanding faculty members UCLA has hired, Sork said, are two at the cutting edge of computational biology: Matteo Pellegrini, professor of molecular, cell and developmental biology, and Xinshu (Grace) Xiao, an associate professor of integrative biology and physiology. Both are in the UCLA College.

From individual genes to entire ecologies

Pellegrini, co-director of the institute, said the move to big data also will enable scientists to significantly broaden the scope of their research.

“We’re going from a paradigm where scientists studied individual genes to one in which they will study organisms and even entire ecologies — sequencing the genomes of communities of organisms and understanding how they interact,” Pellegrini said. “Technology is making science very exciting, presenting enormous opportunities to revolutionize our understanding of biology at the genome-wide level and to apply these techniques to answer all kinds of questions.”

Hoffmann said that in the past, one of the major challenges in biology research was generating data. “Now, the challenge is how to make sense of a tsunami of scientific data, to discover the critical patterns and to tell the signal from the noise,” he said. “The opportunities to develop accurate predictions are unprecedented.”

“These examples are just the tip of the iceberg,” said Hoffmann. “The power of combining big data computational tools with computational modeling based on hard basic science is leading a revolution in the bio- and health sciences that provides unimagined opportunities to humanity.”

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A sense for biosensors


UC Irvine’s Weian Zhao has created a device that improves detection of bacterial, viral invaders in blood samples.

The Integrated Comprehensive Droplet Digital Detection system invented by Weian Zhao of UC Irvine converts blood samples directly into billions of very small droplets. (Photo by Steve Zylius, UC Irvine)

By Tom Vasich, UC Irvine

As a doctoral student at McMaster University in Hamilton, Ontario, Weian Zhao took part in a Canada-wide research effort to develop bioactive paper that would detect, capture and deactivate waterborne and airborne pathogens.

As part of this project, he helped invent gold nanoparticle-coated paper that could detect common pathogens, such as E. coli, but ultimately, the product didn’t meet his exacting standards of diagnostic speed and sensitivity. With a freshly minted Ph.D. in chemistry, Zhao moved on to a joint postdoctoral fellowship at both the Massachusetts Institute of Technology and Harvard, where he dove into stem cell research, his biosensor work seemingly left north of the border.

But the challenge of creating a technology that could rapidly and selectively identify bacterial and viral invaders in blood samples nagged at the young scientist, even as he joined UC Irvine in 2011 as an assistant professor of pharmaceutical sciences with state-of-the-art lab space in the Sue & Bill Gross Stem Cell Research Center.

And then he met Enrico Gratton. In his Laboratory for Fluorescence Dynamics, the UCI biomedical engineer and colleagues have been developing imaging tools for biomedical applications. Among them is a three-dimensional particle counter that tags low-concentration fluorescent particles in large volumes of solution within several minutes, which drew Zhao’s attention. He knew he was back in the biosensor game.

Employing this particle counter, Zhao created a bloodstream infection test that speeds up diagnosis times with unprecedented accuracy – allowing physicians to treat patients with potentially deadly ailments more promptly and effectively.

Zhao says that the Integrated Comprehensive Droplet Digital Detection system can, in as little as 90 minutes, detect bacteria in milliliters of blood with single-cell sensitivity; no cell culture is needed. He published his latest results in the November issue of Nature Communications.

“We are extremely excited about this technology because it addresses a long-standing unmet medical need in the field,” says Zhao, who also holds a faculty appointment in biomedical engineering. “As a platform technology, it may have many applications in detecting extremely low-abundance biomarkers in other areas, such as cancers, HIV and, most notably, Ebola.”

Bloodstream infections are a major cause of illness and death. In particular, infections associated with antimicrobial-resistant pathogens are a growing health problem in the U.S. and worldwide. According to the Centers for Disease Control & Prevention, more than 2 million people a year globally get antibiotic-resistant blood infections, with about 23,000 deaths. The high mortality rate for blood infections is due, in part, to the inability to rapidly diagnose and treat patients in the early stages.

Recent molecular diagnosis methods, including polymerase chain reaction, can reduce the assay time to hours but are often not sensitive enough to detect bacteria that occur at low concentrations in blood, as is common in patients with incipient blood infections.

The Integrated Comprehensive Droplet Digital Detection technology differs from other diagnostic techniques in that it converts blood samples directly into billions of very small droplets. Fluorescent DNA sensor solution infused into the droplets detects those with bacterial markers, lighting them up with an intense fluorescent signal. Zhao says that separating the samples into so many small drops minimizes the interference of other components in blood, making it possible to directly identify target bacteria without the purification typically required in conventional assays.

“The IC 3D instrument is designed to read a large volume in each measurement, to speed up diagnosis,” Gratton says. “Importantly, using this technique, we can detect a positive hit from hundreds of millions of measurement samples with very high confidence.”

But invention was only the first step. Zhao wants to commercialize IC 3D. At UCI, faculty researchers with an entrepreneurial bent can work with the Institute for Innovation, an interdisciplinary and campuswide center focused on integrating research, entrepreneurship and technology to create real-world applications that benefit the public and drive the economy. The Office of Technology Alliances, part of the institute, helped Zhao patent-protect the IC 3D technology and establish a spin-off company, Velox Biosystems, to test and manufacture a commercial IC 3D device.

Currently, Zhao is focusing on applying IC 3D to cancer treatments – an extension of the research he’s been advancing since joining UCI.

Zhao has been developing stem cell messengers that selectively migrate to cancer sites to deliver tumor-fighting drugs or probes for contrast-enhanced medical imaging. This could, potentially, enable the identification of cancer micro-metastases at their early stages and increase the effectiveness of chemotherapeutic treatments for metastatic cancer while mitigating the symptoms associated with systemic chemotherapy.

For this work, Zhao was included in the MIT Technology Review’s 2012 list of the world’s top innovators under the age of 35, and this year he earned a prestigious National Institutes of Health Director’s New Innovator Award to further his efforts to create stem cell-based detection methods and treatments for cancer.

He’s also collaborating with Dr. Jason Zell, an assistant professor of medicine and co-leader of the Colon Cancer Disease-Oriented Team at UCI’s Chao Family Comprehensive Cancer Center, to use IC 3D to identify biomarkers in colon cancers. This could enable oncologists to gauge the effectiveness of treatment during the cancer’s early stages more accurately than with current methods, which Zell says are not reliable.

Zhao is now seeking business partners to accelerate Velox Biosystems’ growth and hopes to conduct clinical studies of IC 3D’s utility in patient diagnosis and treatment.

“That’s what’s so important about this project,” he says. “We’ve created a multi-platform tool that has the potential to work with a variety of infections and diseases. I’m very excited about its future.”

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UC translational medicine leaders chart course


UC BRAID holds annual retreat in San Diego.

UC BRAID program leaders (from left): Jennifer Grandis (UC San Francisco), Lars Berglund (UC Davis), Deborah Grady (UC San Francisco), Steven Dubinett (UCLA), Gary Firestein (UC San Diego) and Dan Cooper (UC Irvine). (Photo by Courtney McFall, UC San Francisco)

By Patti Wieser, UC San Diego

With plans to “think boldly” about the next phase of integrating resources and talent, representatives of the University of California Biomedical Research Acceleration, Integration, and Development (UC BRAID) program staked out future directions during the annual retreat Nov. 7 at UC San Diego. Plans on the horizon include integrating informatics across the UC enterprise, expanding UC Research Exchange (UC ReX – a federated multisite clinical data repository), developing industry partnerships, and expanding the systemwide network for clinical and translational research.

The meeting, which focused on innovation, collaboration and acceleration, drew more than 80 translational medicine researchers, administrative leaders, staff and faculty representing eight UC campuses. The participants also discussed major achievements and potential new areas of focus.

“We are extremely excited about our progress as we continue to create an environment that decreases barriers to biomedical research and creates new tools to facilitate research,” said Gary S. Firestein, M.D., UC BRAID chair, director of UC San Diego Clinical and Translational Research Institute (CTRI) and dean and associate vice chancellor of translational medicine at UC San Diego. “UC BRAID serves as a model for collaborative consortia.”

Established in 2010, UC BRAID, in collaboration with the University of California Office of the President (UCOP), is a joint effort of the five UC biomedical campuses to catalyze, accelerate and reduce the barriers for biomedical, clinical and translational research across the UC system. The UC BRAID consortium — UC Davis, UC Irvine, UCLA, UC San Diego and UC San Francisco — pools data, resources and expertise to reach this goal. UC Riverside, UC Santa Barbara and UC Santa Cruz and UCOP also participated in this year’s UC BRAID meeting.

Lars Berglund, incoming chair of UC BRAID, welcomed the retreat participants. “BRAID is not a goal. It is a means for reaching our goals,” said Berglund, M.D., Ph.D., director of the Clinical and Translational Science Center and senior associate dean of research at UC Davis. The retreat provided a snapshot of “who we are” and energized the participants to continue fulfilling BRAID’s mission. “Enhancing collaboration between the UC system partners will advance the translational research initiative by disintegrating barriers that have evolved,” he said.

Rachael Sak, R.N., M.P.H., director of UC BRAID, discussed the evolvement of UC BRAID during her presentation about leveraging a UC network. “We have a shared vision: to integrate resources and talent across UC to accelerate research that improves health. We are leveraging these, developing Institutional Review Board (IRB) and contracting metrics, and shaping into a collaborative network,” she said. Sak, noting how far the organization has progressed since it was established, cited the following two major successes of UC BRAID during this past year:

Cross-UC clinical trial recruitment: Building upon its accomplishments in cohort discovery and IRB reliance, UC BRAID is developing more advanced cross-campus participant recruitment strategies and services.

National leadership in NIH National Center for Advancing Translational Sciences (NCATS) projects: UC BRAID is at the core of two recent initiatives, Accrual to Clinical Trials and IRB Reliance, supported by NCATS to enable a national network that can conduct large, multicenter clinical trials.

William Tucker, interim vice president of research and graduate studies and executive director of Innovation Alliances and Services with UCOP, presented a talk, “Leveraging UC’s research enterprise for value: President Napolitano’s initiatives that involve research.” Tucker said these initiatives include stimulating research and discovery in areas of strategic importance that benefits California and the world, and improves human lives, the environment and the economy. He lauded BRAID for doing a “great job” of organizing itself and leveraging the system and common practices. Tucker’s takeaway message was: “Think boldly.”

Other presenters were Mike Palazzolo, director of UC BRAID Center for Accelerated Innovation; Doug Bell, chair of UC ReX; Mike Caliguiri, project director for IRB metrics; Eric Mah, project director for IRB reliance; and Dan Dohan, project director for EngageUC. Breakout sessions at the retreat focused on biobanking and biorepositories, child health, contracting, regulatory, drug and device discovery and development, and UC ReX.

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NIH invests in big data to advance biomedical research


Grants awarded to 3 UC campuses: UCLA, UC San Diego and UC Santa Cruz.

The National Institutes of Health has awarded three University of California campuses a total of more than $31 million to develop new strategies for mining and understanding the surge in complex biomedical data sets known as “big data.”

The grants are part of the NIH’s $656 million Big Data to Knowledge, or BD2K, initiative.

UCLA and UC Santa Cruz each were awarded $11 million to form big data computing centers — two of 11 such centers nationwide.

UCLA’s Center of Excellence for Big Data Computing will create analytic tools to address the daunting challenges facing researchers in accessing, standardizing and sharing scientific data to foster new discoveries in medicine. Investigators also will train the next generation of experts and develop data science approaches for use by scientists. The center’s principal investigator will be Peipei Ping, a professor of physiology, medicine and bioinformatics at the David Geffen School of Medicine at UCLA.

The Center for Big Data in Translational Genomics, a multi-institutional partnership based at UC Santa Cruz, will help the biomedical community use genomic information to better understand human health and disease. The center will be led by David Haussler, professor of biomolecular engineering and director of the UC Santa Cruz Genomics Institute.

In addition, UC Irvine assistant professor of psychiatry & human behavior Theo van Erp is co-chair of the schizophrenia working group for the Enhancing Neuro Imaging Genetics Through Meta-Analysis project. Led by the University of Southern California, the ENIGMA Center for Worldwide Medicine, Imaging and Genomics received an $11 million Big Data to Knowledge grant. UCLA also is particpating in the ENGIMA consortium, with its research led by Carrie Bearden, professor of psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior, and Eleazar Eskin, professor of computer science and human genetics.

Also, researchers at the UC San Diego School of Medicine have been awarded a $9.2 million grant to help modernize and transform how researchers share, use, find and cite biomedical datasets. UC San Diego professor of medicine Lucila Ohno-Machado will be lead investigator on the Biomedical and healthCAre Data Discovery and Indexing Ecosystem (BioCADDIE), a 3-year project, in collaboration with The University of Texas Health Science Center at Houston.

“Data creation in today’s research is exponentially more rapid than anything we anticipated even a decade ago,” said NIH Director Francis S. Collins. “Mammoth data sets are emerging at an accelerated pace in today’s biomedical research and these funds will help us overcome the obstacles to maximizing their utility. The potential of these data, when used effectively, is quite astounding.”

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NIH awards high-risk, high-reward research grants


UC researchers receive 17 of 85 awards aimed at innovative approaches to biomed research.

Michi Taga,UC Berkeley

The National Institutes of Health awarded 85 grants under its High Risk-High Reward program, of which 17 will go to University of California researchers. The awards support scientists proposing highly innovative approaches to major contemporary challenges in biomedical research.

UC researchers received 11 of 50 New Innovator awards, which support projects by early-career biomedical researchers with the potential to transform scientific fields and accelerate the translation of research into new ways to improve human health.

UC scientists also received:

  • One of 10 Pioneer awards for groundbreaking approaches that have the potential to make an unusually high impact on a broad area of biomedical or behavioral research;
  • Two of eight Transformative Research awards for cross-cutting interdisciplinary approaches that could potentially create or challenge existing paradigms; and
  • Three of 17 Early Independence awards that provide an opportunity for exceptional junior scientists to skip traditional postdoctoral training and move immediately into independent research positions.

“Supporting innovative investigators with the potential to transform scientific fields is a critical element of our mission,”’ said NIH Director Francis S. Collins. “This program allows researchers to propose highly creative research projects across a broad range of biomedical and behavioral research areas that involve inherent risk but have the potential to lead to dramatic breakthroughs.”

The total funding for the 85 grants is approximately $141 million.

Weian Zhao, UC Irvine

UC recipients include:

UC Berkeley

  • Nicholas Ingolia (New Innovator)
  • Michi Taga (New Innovator)
  • Roberto Zoncu (New Innovator)

UC Davis

  • Lin Tian (New Innovator)

UC Irvine

  • Weian Zhao (New Innovator)

UCLA

  • Reza Ardehali (New Innovator)
  • Elissa Hallem (New Innovator)
  • Sriram Kosuri (New Innovator)
  • Lili Yang (New Innovator)

UC San Francisco

  • Adam Abate (New Innovator)
  • Robert Judson (Early Independence)
  • Wendell Lim (Transformative Research)
  • Michael McManus (Transformative Research)
  • Michael Rosenblum (New Innovator)
  • Glenn-Milo Santos (Early Independence)

UC Santa Barbara

  • Denise Montell (Pioneer)

Lawrence Livermore National Laboratory

  • Amanda Randles (Early Independence)

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UCSF Discovery Fellows Program meet fundraising challenge


Strong show of support for basic science education and research.

Members of the inaugural class of Discovery Fellows are joined by philanthropist Harriet Heyman. (Photo by Elisabeth Fall)

A year ahead of schedule, UC San Francisco has met the unprecedented fundraising challenge set by Sir Michael Moritz and Harriet Heyman to raise $5 million from 500 donors for the Discovery Fellows Program, which supports basic science Ph.D. education.

Moritz and Heyman responded to the news that their challenge had been met by extending the fundraising effort through 2016 with up to $5 million more in matching funds, and by committing a $1 million bonus if the new campaign attracts another 500 donors.

“Strength and purpose depend on communities deciding to attack the future with gusto,” said Moritz, chairman of Sequoia Capital in Menlo Park. “This has happened in a spectacular manner at UCSF during the last year, and we hope that even more people now have a great, additional incentive to help our university attract medical science’s most talented graduate students.”

At $60 million, the Discovery Fellows Program is already the largest endowed Ph.D. education program in the history of the University of California system. The couple launched it last year with a $30 million gift, which was matched by UCSF and hundreds of individuals, most of whom gave to the university for the first time.

The fund recognizes the critical role doctoral students play in fueling biomedical research. As the endowment grows, it will increasingly take the financial pressure off faculty to fund education with research money and give students freedom to choose their mentors based on scientific rather than financial concerns.

“This endowment will support basic science at UCSF for generations to come,” said Elizabeth Watkins, Ph.D., dean of the Graduate Division and vice chancellor of student academic affairs. “It goes to the very heart of what UCSF is all about: creating the conditions for scientists to do great work.”

A spate of generous donations from UCSF friends and alumni helped propel the campaign to success. Among the donors who made leadership gifts to establish named fellowships are the philanthropist Hwalin Lee, Ph.D., class of ’66; former UCSF Chancellor Susan Desmond-Hellmann, M.D., M.P.H., and her husband Nicholas Hellmann, M.D.; retired Impax Laboratories Inc. chief Larry Hsu, Ph.D.; and Pablo Valenzuela, Ph.D., co-founder of Chiron Corp., and his wife Bernadita Valenzuela, Ph.D.

Lee, who received his doctorate from UCSF, said he gave to express his appreciation for his alma mater. “I think this is a very good opportunity to do something for the school,” he said.

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National Biomedical Computation Resource receives $9M from NIH


Collaborative effort crosses disciplines to advance biomedical research.

Rommie Amaro, UC San Diego

The National Biomedical Computation Resource (NBCR) at UC San Diego has received $9 million in funding from the National Institutes of Health (NIH). The funding will allow NBCR to continue its work connecting biomedical scientists with supercomputing power and emerging information technologies.

National Biomedical Computation Resource Director Rommie Amaro says renewed funding from the Naitonal Institutes of Health will make it possible for biomedical researchers to study phenomena from the molecular level to the level of the whole organ.

Biomedical computation – which applies physical modeling and computer science to the field of biomedical sciences – is often a cheaper alternative to traditional experimental approaches and can speed the rate at which discoveries are made for host of human diseases and biological processes.

The five-year NIH grant from the National Institute of General Medical Sciences provides funding for everything from staffing and training to developing biomedical research technologies for academic researchers around the world. It involves faculty from UC San Diego’s Physical Sciences, School of Medicine, Jacobs School of Engineering, San Diego Supercomputer Center (SDSC), as well as faculty from The Scripps Research Institute (TSRI), a private, nonprofit research organization.

“NBCR has evolved tremendously in the 21 years since it was created,” said Amaro, an associate professor of chemistry and biochemistry at UC San Diego and an affiliate of the UC San Diego Qualcomm Institute (QI). “Our main effort remains focused on making connections across diverse scales of biological organization. As scientists, we are very good at looking at particular components of the human body within a single scale, but we ultimately need to connect across three or four scales in order to model and understand complex biological phenomena from the molecular level minutia all the way up to the whole organ.”

NBCR is run under the auspices of the UC San Diego Center for Research in Biological Systems at QI. It provides a collection of computational tools – Web services, graphical models, simulation methods and technologies and workflows – that make it possible for, say, a molecular biologist or neuroscientist to extrapolate how the molecular dynamics in brain cells might affect the whole organ.

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NIH awards $2M for DNA sequencing research


UC Santa Cruz leads efforts to develop nanopore technology for DNA sequencing.

Mark Akeson, UC Santa Cruz

A group led by Mark Akeson, professor of biomolecular engineering at UC Santa Cruz, will receive $2.29 million over three years from the National Human Genome Research Institute (NHGRI) to support the team’s work on novel DNA sequencing technology.

Akeson leads the UC Santa Cruz nanopore group, which has spent years developing technology to analyze DNA strands as they pass through a tiny pore in a membrane, called a “nanopore” because it is just 1.5 nanometers wide at its narrowest point. (A nanometer is one billionth of a meter; a human hair is about 100,000 nanometers wide.) Akeson’s group has made important advances in nanopore sequencing technology, and research funded by the new grant could have valuable applications in biomedical research.

The project will focus on optimization of enzymes, pores and computational methods for nanopore sequencing of individual DNA molecules taken directly from the nucleus of a cell. The UCSC group uses a nanopore formed by a self-assembling protein complex called an ion channel, inserted into a membrane similar to a cell membrane. An electric field drives DNA strands (which are negatively charged) through the nanopore, and blockage of the nanopore as a strand passes through produces electrical current modulations that can be analyzed to yield DNA sequence information.

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Squid skin protein could improve biomedical technologies


Conductivity could charge up futuristic disease treatments.

A protein in squid skin called reflectin can conduct positive electrical charges, making it a useful in helping medical devices communicate with the human system. (Image by Matt Woodworth)

The common pencil squid (Loliginidae) may hold the key to a new generation of medical technologies that could communicate more directly with the human body. UC Irvine materials science researchers have discovered that reflectin, a protein in the tentacled creature’s skin, can conduct positive electrical charges, or protons, making it a promising material for building biologically inspired devices.

Currently, products such as retinal implants, nerve stimulators and pacemakers rely on electrons – particles with negative charges – to transmit diagnosis data or to treat medical conditions. Living organisms use protons, with positive charges, or ions, which are atoms that contain both electrons and protons, to send such signals. The UC Irvine discovery could lead to better ion- or proton-conducting materials: for instance, next-generation implants that could relay electrical messages to the nervous system to monitor or interfere with the progression of disease.

Alon Gorodetsky, assistant professor of chemical engineering & materials science at The Henry Samueli School of Engineering, led the research team. “Nature is really good at doing certain things that we sometimes find incredibly difficult,” he said. “Perhaps nature has already optimized reflectin to conduct protons, so we can learn from this protein and take advantage of natural design principles.”

He and his group have been studying reflectin to discern how it enables squid to change color and reflect light. They produced the squid protein in common bacteria and used it to make thin films on a silicon substrate. Via metal electrodes that contacted the film, the researchers observed the relationship between current and voltage under various conditions. Reflectin transported protons, they found, nearly as effectively as many of the best artificial materials.

Gorodetsky believes reflectin has several advantages for biological electronics. Because it’s a soft biomaterial, reflectin can conform to flexible surfaces, and it may be less likely to be rejected by the human body. In addition, protein engineering principles could be utilized to modify reflectin for very specific purposes and to allow the protein to decompose when no longer needed.

“We plan to use reflectin as a template for the development of improved ion- and proton-conducting materials,” Gorodetsky said. “We hope to evolve this protein for optimum functionality in specific devices – such as transistors used for interfacing with neural cells – similar to how proteins evolve for specific tasks in nature.”

The research is published in the July issue of Nature Chemistry. Co-authors are David Ordinario, Long Phan, Ward Walkup, Jonah-Micah Jocson, Emil Karshalev and Nina Husken of UC Irvine.

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UC BRAID holds annual retreat


UC translational medicine leaders celebrate achievements with eye toward future.

UC BRAID program leaders (from left) Clay Johnston, UC San Francisco; Dan Cooper, UC Irvine; Gary Firestein, UC San Diego; Lars Berglund, UC Davis; and Steven Dubinett, UCLA, with Steven Beckwith, vice president for research and graduate studies at the UC Office of the President. (Photo by Christina McCabe, UC San Diego)

UC BRAID program leaders (from left) Clay Johnston, UC San Francisco; Dan Cooper, UC Irvine; Gary Firestein, UC San Diego; Lars Berglund, UC Davis; and Steven Dubinett, UCLA, with Steven Beckwith, vice president for research and graduate studies at the UC Office of the President.

By Patti Wieser

The path forward is clear: To continue and enhance the development of a robust coordinating center that combines the individual University of California health campuses into a model virtual biomedical research institution.

That’s the conclusion reached by representatives of the University of California Biomedical Research Acceleration, Integration, and Development (UC BRAID) program during an annual retreat held at UC San Diego on Oct. 15. About 70 translational medicine researchers, administrative leaders, staff and faculty representing seven UC campuses met to discuss next steps along the path, identify potential research intersections and share the achievements for UC BRAID.

“The largest role for BRAID is enabling partnerships, and that will help us reach our goal of reducing barriers to biomedical research,” said Gary S. Firestein, M.D., UC BRAID chair, director of UC San Diego’s Clinical and Translational Research Institute, and dean and associate vice chancellor of translational medicine at UC San Diego.

Established in 2010, UC BRAID, in collaboration with the University of California Office of the President, is a joint effort of the five UC biomedical campuses to catalyze, accelerate and reduce the barriers for biomedical, clinical and translational research across the UC system. The UC BRAID consortium — UC Davis, UC Irvine, UCLA, UC San Diego and UC San Francisco — pools data, resources and expertise to reach this goal. UC Riverside and Santa Cruz also participated in this year’s UC BRAID meeting.

Major successes of UC BRAID highlighted at the 2013 retreat were:

UC-Research eXchange consortium (UC-ReX): UC BRAID launched the consortium’s first tool from UC ReX, namely the Data Explorer, building the first cross-campus clinical query system capable of exchanging patient-level data, as well as aggregates (counts and descriptive statistics). The UC ReX Data Explorer enables search of 12 million de-identified patient records from the five UC medical centers with one query.

U54 Center for Accelerated Innovation (CAI): NIH’s National Heart, Lung and Blood Institute awarded $12 million to UC to create a Center for Accelerated Innovation (CAI). UC BRAID oversees this new center aimed at translating innovations into improved health.

“An important part of UC BRAID’s mission is to improve UC collaborative research opportunities. UC ReX is a great example of how UC BRAID accomplishes this,” said Firestein, who went on to laud the CAI as a UC BRAID accomplishment. “The new U54 CAI is a remarkable example of inter-institutional collaboration.” Michael Palazzolo, M.D., a professor of medicine at UCLA, is the principal investigator for CAI.

Firestein and UC BRAID Director Rachael Sak, R.N., M.P.H., gave presentations about how UC BRAID takes research from silos to collaboration and how to leverage the program. Firestein cited examples of silos in academic medicine as multiple cores performing the same service, different IT systems in clinical research and resistance to central institutional review boards.

He emphasized the urgency of change, building a guiding team and getting the vision right. “We must empower change, remove obstacles and reward progress,” the UC BRAID chair said.

Clay Johnston, M.D., a member of the UC BRAID Executive Committee, added that UC BRAID realizes its vision by identifying areas of collaboration, aligning across multicampus initiatives, and evaluating priorities and making funding recommendations. “We were established to identify and address, on a systemwide level, the shared challenges of academic translational science,” Johnston said.

Other key topics at the retreat included biorepositories, contracting, regulatory, and drug and device discovery and development. Participants also discussed the new BRAID Child Health Initiative to expand research for the pediatric population. The presentations and agenda are available at: www.ucbraid.org/events.html.

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NIH official says spending cuts pose threat to biomedical research


Sally Rockey: “When you put money behind an issue or disease, you can move rapidly.”

Sally Rockey of the National Institutes of Health talks with UCSF scientist Tejal Desai during a tour at UCSF Mission Bay.

Sally Rockey of the National Institutes of Health talks with UCSF scientist Tejal Desai during a tour at UCSF Mission Bay.

Scientific progress and innovation are speeding along, faster than ever before, but arbitrary spending cuts are posing an unprecedented threat.

That’s the sobering paradox of biomedical research according to Sally Rockey, PhD, a high-ranking official at the National Institutes of Health (NIH), who visited UC San Francisco last week.

Rockey, Ph.D., deputy director for extramural research at the NIH, oversees about $25 billion in grants, which represent more than 80 percent of the NIH budget.

The title of her address says it all: “NIH: Interesting Times, Challenging Times.”

She spoke of the astounding impact of biomedical research on U.S. health: The cancer rate is falling about 1 percent a year. Death rates for cardiovascular disease have dropped 60 percent in the last half-century. And HIV therapies are enabling people in their 20s infected with the virus to live to age 70 and beyond.

“It demonstrates that when you put money behind an issue or disease, you can move rapidly,” Rockey said, adding that it also shows that NIH-supported research on retroviruses provided a knowledge base when the AIDS epidemic surfaced.

Rockey showed a photograph of the enormous campus of the NIH, which has 17,000 federal employees and another 20,000 contractors. It funds about 25,000 institutions and organizations at any given time, and between 300,000 and 400,000 individuals.

About one of every 500 members of the U.S. working population is in some way supported by the NIH, said Rockey, who was acutely mindful of the possibility of the looming government shutdown that has since become a reality.

Between 1998 and 2003, the NIH budget more than doubled, from $13 billion to $27 billion. But now it has flattened, Rockey said, and about 25 percent of its buying power has been lost because of the increased cost of research.

“We’ve been flat for a long time, and this becomes problematic for us,” said Rockey, who appeared Sept. 24 at Genentech Hall on the UCSF Mission Bay campus. “What really becomes problematic – and the thing that you all feel – is the reduction in the success rate.”

The rate – the number of awards divided by the number of applications – was 17.8 percent in 2012, “really low” compared with a historic high of 30 percent.

“What does this mean?” Rockey asked. “This is a really tough time to think about the future of individuals considering a future in biomedical research, because they know they have only a 15 percent chance of getting funded and there’s a lot of work that goes into putting these proposals together.”

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NIH awards high-risk, high-reward research grants


UC scientists receive 15 awards.

(From left) Ali Mortazavi, Sunil Gandhi and Aaron Esser-Kahn of UC Irvine are among 15 UC and UC-affiliated scientists receiving awards to support innovation in biomedical research.

(From left) Ali Mortazavi, Sunil Gandhi and Aaron Esser-Kahn of UC Irvine are among 15 UC scientists receiving awards to support innovation in biomedical research.

University of California researchers received 15 of 78 National Institutes of Health awards announced today (Sept. 30) for high-risk, high-reward research.

That includes nine of 41 NIH Director’s New Innovator Awards, four of 15 NIH Director’s Early Independence Awards and two of 12 NIH Pioneer Awards. The NIH also awarded 10 Transformative Research Awards. The total NIH funding for the 78 awards is approximately $123 million.

The New Innovator Awards support projects by early-career researchers that show potential to transform scientific fields and accelerate the translation of research into new ways to improve human health. The work by UC researchers could aid in the development of safer, more targeted vaccines; help in repairing damage caused by traumatic brain injury, stroke or neurodegenerative disease; and help lead to a way to keep HIV-infected people from developing AIDS without a lifelong need for antiretroviral drugs.

Pioneer Awards challenge investigators at all career levels to develop highly innovative approaches that could have a powerful impact on a broad area of biomedical or behavioral research. Early Independence Awards provide an opportunity for exceptional junior scientists who recently have received their doctoral degree or finished medical residency to skip traditional postdoctoral training and move immediately into independent research positions.

UC recipients include:

UC Berkeley

  • Hillel Adesnik, NIH Director’s New Innovator Award
  • Jennifer Ahern, NIH Director’s New Innovator Award
  • William Ludington, NIH Director’s Early Independence Award
  • David Frank Savage, NIH Director’s New Innovator Award

UC Irvine

  • Aaron Palmer Esser-Kahn, NIH Director’s New Innovator Award
  • Sunil Gandhi, NIH Director’s New Innovator Award
  • Seyed Ali Mortazavi, NIH Director’s New Innovator Award

UCLA

  • Baljit Khakh, NIH Pioneer Award

UC San Diego

  • Hannah Kathryn Carter, NIH Director’s Early Independence Award

UC San Francisco

  • Rahul Chandrakant Deo, NIH Director’s New Innovator Award
  • Zev Jordan Gartner, NIH Director’s New Innovator Award
  • Lei Stanley Qi, NIH Director’s Early Independence Award
  • Shomyseh Sanjabi, NIH Director’s New Innovator Award
  • David Eric Weinberg, NIH Director’s Early Independence Award
  • Leor S. Weinberger, NIH Pioneer Award

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