TAG: "Biotechnology"

Berkeley’s Jennifer Doudna among Time magazine’s 100 most influential people

List of most influential in world range from President Barack Obama to rapper Kanye West.

UC Berkeley professor Jennifer Doudna, left, has been named among Time magazine's 100 most influential people

By Robert Sanders, UC Berkeley

Time magazine has named Jennifer Doudna, a professor of molecular and cell biology, to its 2015 list of the 100 most influential people in the world.

The list, now in its 12th year, recognizes the activism, innovation and achievement of the world’s most influential individuals.

Doudna is in the company of honorees such as President Barack Obama, Supreme Court Justice Ruth Bader Ginsburg, Russian President Vladimir Putin, German Chancellor Angela Merkel, Democratic presidential hopeful Hillary Clinton, author Haruki Murakami, Apple CEO Tom Cook and rapper Kanye West.

A Howard Hughes Medical Institute investigator at UC Berkeley, Doudna has received numerous honors and awards for her discovery of a revolutionary DNA-editing technique that has upended the world of genetics. The technique, called CRISPR-Cas9, exploits precisely targeted DNA-cutting enzymes from bacteria to snip and edit human and animal DNA, making it much easier to create animal models of disease and possibly correct human genetic disease via gene therapy.

Her colleague and co-discoverer, Emmanuelle Charpentier of the Helmholtz Center for Infection Research and Umeå University, was also named to Time‘s 100 list.

“Their technique, CRISPR-Cas9, gives scientists the power to remove or add genetic material at will,” wrote geneticist Mary-Claire King in a summary of their work. “Working with cells in a lab, geneticists have used this technology to cut out HIV, to correct sickle-cell anemia and to alter cancer cells to make them more susceptible to chemotherapy. With CRISPR-Cas9, a scientist could, in theory, alter any human gene. This is a true breakthrough, the implications of which we are just beginning to imagine.”

King discovered the BRCA1 breast cancer gene while a professor at UC Berkeley in the 1990s, before moving to the University of Washington, Seattle.

Time editor Nancy Gibbs several years ago explained that “The Time 100 is a list of the world’s most influential men and women, not its most powerful, though those are not mutually exclusive terms …. While power is certain, influence is subtle…. As much as this exercise chronicles the achievements of the past year, we also focus on figures whose influence is likely to grow, so we can look around the corner to see what is coming.”

The full list and related tributes to the Time 100 appear in the April 27 issue of the magazine, available online today (April 16) and at newsstands and for tablets on Friday, April 17.

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Unlocking the key to immunological memory in bacteria

Powerful genome editing tool may become more powerful.

By Lynn Yarris, Berkeley Lab

A powerful genome editing tool may soon become even more powerful. Researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) have unlocked the key to how bacteria are able to “steal” genetic information from viruses and other foreign invaders for use in their own immunological memory system.

“We’ve shown that bacteria need only two proteins to facilitate this process, Cas1 and Cas2,” says Jennifer Doudna, a biochemist with Berkeley Lab’s Physical Biosciences Division. “Our findings could provide an alternative way of introducing needed genetic information into a human cell or correcting a problem in an existing genome.”

Doudna, who also holds appointments with the University of California Berkeley’s Department of Molecular and Cell Biology and Department of Chemistry, and is also an investigator with the Howard Hughes Medical Institute (HHMI), is the corresponding author of a paper in Nature that describes the research. The paper is titled “Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity.” The lead author is James Nuñez, a member of Doudna’s UC Berkeley research group. Other authors are Amy Lee and Alan Engelman.

Bacteria face a never-ending onslaught from viruses and invading strands of nucleic acid known as plasmids. To survive this onslaught, bacteria and archaea deploy a variety of defense mechanisms, including an adaptive-type immune system that revolves around a unit of DNA known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. A CRISPR unit of DNA is made up of “repeat” elements, base-pair sequences ranging from 30 to 60 nucleotides in length, separated by “spacer” elements, variable sequences that are also from 30 to 60 nucleotides in length.

Through the combination of CRISPR and squads of CRISPR-associated – “Cas” – proteins, bacteria are able to utilize small customized RNA molecules to silence critical portions of a foreign invader’s genetic message and acquire immunity from similar invasions in the future by “remembering” prior infections. Doudna and her research group have been pioneers in unraveling the mysteries behind the CRISPR-based immunological memory of bacteria.

“We’ve learned that bacteria can acquire critical pieces of genetic information from foreign invaders and insert this information into the CRISPR loci within their own genome as new spacers,” Nuñez says. “These foreign-derived spacers basically function as a memory bank.”

Until now, however, it was not known how spacers are stolen from the foreign invader’s genome and transferred into the CRISPR loci of the host. Working with the bacteria E. coli and using high-through­put sequencing of spacers inserted in vitro, Doudna, Nuñez and their colleagues found that the memorizing proteins – Cas1 and Cas2 – recognize repeating sequences in CRISPR loci and target these sites for the spacer insertion process.

“Repeat sequences in a host bacterium’s CRISPR locus form DNA cruciform (cross-shaped) structures that recruit Cas1 and Cas2 to the site for the insertion of spacer sequences,” Nuñez says. “The cruciform structures tell Cas1 and Cas2 precisely where to place the spacer sequences from a foreign invader, a virus or a plasmid. When the process is completed, the host bacterium is now immune to future infections from that same type of virus or plasmid.”

Doudna and her group believe that it may be possible in the future to program Cas1 and Cas2 proteins with a DNA sequence that carries desired information, i.e., codes for a specific protein, then insert this DNA into the appropriate site in the genome of a human cell using additional Cas1 and Cas2 proteins.

“It turns out that bacteria and archaea have been using Cas1 and Cas2 proteins in their immunization process for millions of years,” says Nuñez. “Our next task is to figure out the rules behind the process and how to apply them to human cells.”

This research was supported by grants from the National Science Foundation and the National Institutes of Health.

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High school students help grow ‘genetically engineered machine’

UCSF researchers help high school students dive into growing field of synthetic biology.

In addition to their prize-winning science project, the 2014 UCSF iGEM team morphed into superheroes as a creative way to teach synthetic biology to visitors at The Exploratorium.

By Kathleen Masterson, UC San Francisco

Taking molecular parts from living organisms to engineer biological systems sounds a bit like science fiction, but with the help of UCSF researchers, high school students are diving into this growing field of synthetic biology.

It’s all part of a global synthetic biology competition called iGEM.

The international competition aims to engage students in the constantly evolving world of synthetic biology, which is part molecular biology, part systems biology and part genetic engineering. While the “Giant Jamboree” is a fun, lively event, the lab work and presentation preparation are serious work – and real science findings come out of the competition.

This year UCSF’s team won “Best Presentation,” competing against 225 teams hailing from across the globe. Of the two UCSF presenters, one was Eleanor Amidei, who was 17 years old at the time.

To prepare for the competition, the students spend all summer designing their experiments, running them, building a website, developing a presentation and a few other requirements, including submitting a genetic fragment to the synthetic biology bank at MIT.

“At first it was really overwhelming,” said Amidei, who is now a freshmen at UC Berkeley. “It was just scary to be thrown into lab environment. But you kind of just pick up the work as you’re going; you go with it, you read articles, you study more about what you’re doing and it becomes easy, it becomes second nature.”

Bringing high schoolers into the lab

When Wendell Lim, Ph.D., formed the first UCSF team eight years ago, he needed to include participants younger than graduate students to meet the iGEM contest eligibility requirement. Instead of bringing in college students, he partnered with high school teacher George Cachianes who teaches a two-year biotechnology program at Lincoln High School in San Francisco. Every year, a few of the top high school students are invited to join the iGEM team.

This year’s team also partnered with two UC Berkeley undergrads who bring additional programming and graphic design elements to the team skill set.

Lim said the experience benefits both the high school students and the Ph.D. students, who learn to be better mentors.

“What is really unique about this experience is that most of the time, when you do an internship in a lab, you’re assigned to one person who tells you what to do, who gives you instructions,” he said.

But here the group is really a team, said Lim. There’s a lot of brainstorming, and the students, few undergrads, postdocs, all really work together to shape the project. “We’ve defined the sandbox we’ll play in, but exactly what we do and how we do it – they’re a part of defining.”

Real science findings

This year the “sandbox” focused on testing yeast cells to determine if they exhibit collective behavior. That’s a loose term for the “group think” behavior exhibited by seemingly choreographed flocks of birds or tightly synchronized schools of fish swirling in a flash. This kind of group response also occurs in some cells and even electrons – and in tiny yeast cells.

The team discovered that the presence of the group actually influences the behavior of the yeast cells. Though the cells are genetically the same, they respond differently when isolated and respond in synchronized manner when together as a group.

This behavior hadn’t been shown in yeast, said Kara Helmke, the education and outreach coordinator for UCSF’s Center for Systems and Synthetic Biology who works with the iGEM teams.

“The findings were something we didn’t even realize would be possible,” Helmke said. “It was great we could demonstrate it.”

Beyond getting results in the lab, the UCSF team is producing new scientists: Of the more than 60 high school alumni of the program, all are pursuing or have completed science degrees.

“Biotechnology is really a unique aspect of San Francisco and important part of the economy, and it’s exciting to help train the next generation of people,” said Helmke.

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Chemists find a way to unboil eggs

Ability to quickly restore molecular proteins could slash biotechnology costs.

Chemistry major Stephan Kudlacek and professor Greg Weiss have developed a way of unboiling a hen egg. (Photo by Steve Zylius, UC Irvine)

By Janet Wilson, UC Irvine

UC Irvine and Australian chemists have figured out how to unboil egg whites – an innovation that could dramatically reduce costs for cancer treatments, food production and other segments of the $160 billion global biotechnology industry, according to findings published today (Jan. 23) in the journal ChemBioChem.

“Yes, we have invented a way to unboil a hen egg,” said Gregory Weiss, UCI professor of chemistry and molecular biology & biochemistry. “In our paper, we describe a device for pulling apart tangled proteins and allowing them to refold. We start with egg whites boiled for 20 minutes at 90 degrees Celsius and return a key protein in the egg to working order.”

Like many researchers, he has struggled to efficiently produce or recycle valuable molecular proteins that have a wide range of applications but which frequently “misfold” into structurally incorrect shapes when they are formed, rendering them useless.

“It’s not so much that we’re interested in processing the eggs; that’s just demonstrating how powerful this process is,” Weiss said. “The real problem is there are lots of cases of gummy proteins that you spend way too much time scraping off your test tubes, and you want some means of recovering that material.”

But older methods are expensive and time-consuming: The equivalent of dialysis at the molecular level must be done for about four days. “The new process takes minutes,” Weiss noted. “It speeds things up by a factor of thousands.”

To re-create a clear protein known as lysozyme once an egg has been boiled, he and his colleagues add a urea substance that chews away at the whites, liquefying the solid material. That’s half the process; at the molecular level, protein bits are still balled up into unusable masses. The scientists then employ a vortex fluid device, a high-powered machine designed by Professor Colin Raston’s laboratory at South Australia’s Flinders University. Shear stress within thin, microfluidic films is applied to those tiny pieces, forcing them back into untangled, proper form.

“This method … could transform industrial and research production of proteins,” the researchers write in ChemBioChem.

For example, pharmaceutical companies currently create cancer antibodies in expensive hamster ovary cells that do not often misfold proteins. The ability to quickly and cheaply re-form common proteins from yeast or E. coli bacteria could potentially streamline protein manufacturing and make cancer treatments more affordable. Industrial cheese makers, farmers and others who use recombinant proteins could also achieve more bang for their buck.

UCI has filed for a patent on the work, and its Office of Technology Alliances is working with interested commercial partners.

Besides Weiss and Raston, the paper’s authors are Tom Yuan, Joshua Smith, Stephan Kudlacek, Mariam Iftikhar, Tivoli Olsen, William Brown, Kaitlin Pugliese and Sameeran Kunche of UCI, as well as Callum Ormonde of the University of Western Australia. The research was supported by the National Institute of General Medical Sciences (grant R01 GM100700-01) and the Australian Research Council (grants DP1092810 and DP130100066).

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Recently identified molecule could lead to new tendon repair

Berkeley Lab scientists study cell-density signaling complex linked to collagen production.

It’s an all-too familiar scenario for many people. You sprain your ankle or twist your knee. If you’re an adult, the initial pain is followed by a long road of recovery, with no promise that the torn ligament or tendon will ever regain its full strength.

That’s because tendon and ligament cells in adults produce little collagen, the fibrous protein that is used to build new tendon and ligament tissue. Physical therapy and surgery help, but for many people, there may always be a nagging reminder of the injury.

But what if doctors could coax an injured tendon to regenerate itself back to its original strength? A solution along these lines may come from an unlikely, feathered source. Berkeley Lab scientists have identified a molecule that guides the formation of tendons and ligaments. And they found it in chicken embryos.

The molecule binds to the outer lipid membrane of tendon cells, and allows tendon cells to signal their presence to other cells. The molecule’s job is to orchestrate growth and collagen production. In a chicken embryo, a dense growth plate of tendon cells work together to spin out collagen and weave new tendon, which is basically a collagen rope. The more cells signaling their presence to each other, the more collagen is produced.

The gene that expresses the protein component of this signaling molecule is highly conserved among animals, meaning a similar molecule performs the same tendon-building job in developing humans.

“More research is needed, but our initial experiments suggest this protein-phospholipid molecule could be administered to adults who’ve had tendon injuries, to spark healthy tendon growth in the same way that happens during embryogenesis,” says Richard Schwarz of Berkeley Lab’s Life Sciences Division, a biologist who leads this research.

Schwarz studied chickens because they’re stars when it comes to making tendons. Chicken embryos start developing tendons just eleven days before hatching, and they enter the world ready to skitter about for food.

“Their tendon-growth process is very fast,” says Schwarz.

The process isn’t nearly as fast in humans, but the idea is the same. When we’re growing, the tendon cells in growth plates are densely packed together, the perfect conditions for collagen production. In adults, however, the growth plates recede and the few remaining tendon cells are at low cell density. They produce enough collagen to maintain tendons, but not enough to repair an injured tendon.

“In adults, tendon repairs are more like darning a sock — adequate, but not like new,” says Schwarz.

Schwarz’s idea is to reignite the tendon-building capability that occurs during embryogenesis and throughout childhood.

“If we could add back this growth factor, then we could make tendon cells believe they are at high density again — and cause them to reform this growth plate,” says Schwarz.

Initial experiments on cell cultures have proved promising, but Schwarz says that more research is needed. For example, one big question that needs to tested in vivo is whether adult tendon can be driven to form a new growth plate — and heal the tendon or ligament in a stronger and faster manner — by injecting a tendon cell-density signal.

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What about BOB?

Berkeley Lab proposal for an open biofoundry passes crucial first test.

BOB, the Berkeley Open Biofoundry, would be housed in the EmeryStation East building in Emeryville along with DOE’s Joint BioEnergy Institute.

Picture an industrial-sized manufacturing plant in which workers are turning out a valuable chemical product, say a pharmaceutical drug, or an exotic material such as a truly biodegradable plastic, or a clean-burning carbon-neutral transportation fuel. Now picture that plant as being void of smokestacks venting carbon dioxide into the atmosphere, or receptacles for the collecting of toxic, non-recyclable waste. This is the promise of biomanufacturing, in which biological organisms or systems are used to make desired molecules, and it has the potential to become one of the defining technologies of the 21st century.

A Berkeley Lab proposal submitted to the Defense Advanced Research Projects Agency (DARPA) for the establishment of a scientific center for biomanufacturing has passed a crucial first test. DARPA has awarded Berkeley Lab $1.5 million to proceed with a “Task Area 1” (TA1) design and study phase for what is being called “BOB” – for Berkeley Open Biofoundry. By providing the science and technology that will enable the engineering of biological systems to produce valuable chemical products on a commercial scale, BOB is conceived to do for biology what the Molecular Foundry does for nanomaterials.

“The idea behind BOB is to create a new type of user facility in which industrial, academic and government stakeholders will have access to engineered biological systems, including microbes, plants and tissues, at all stages of the engineering process, including design, building, testing and learning,” says Mary Maxon, the head of strategic planning and development for biosciences at Berkeley Lab who is spearheading this proposal along with Jay Keasling, Berkeley Lab’s associate lab director for biosciences. “BOB represents an important step along a pathway that will ultimately lead to a biomanufacturing center for excellence. This center of excellence is envisioned to be a Silicon Valley-style ecosystem of engineering for biology where designs and start-up systems are created but manufacturing is done elsewhere.”

Manufacturing is defined as the human transformation of materials from one form to another, more valuable form. Whereas many traditional manufacturing processes deplete natural resources and damage the environment, biomanufacturing can be both sustainable and environmentally benign. The primary challenges to biomanufacturing have been complexity and cost. Despite these challenges, biomanufacturing now accounts for more than $190 billion annually in U.S. revenues, with California, the birthplace of genetic engineering, accounting for roughly 22 percent of that figure.

“Biomanufacturing could be a significantly larger fraction of the U.S. economy if biology were easier and cheaper to engineer,” says Keasling, who provided a look into what biomanufacturing can offer with the engineering of a strain of yeast that can be used to produce artemisinin, the world’s most powerful anti-malaria drug. When exclusively produced from the wormwood plant, the supply of artemisinin was unreliable and its price too high for the people in developing nations who need it most. With the arrival of a microbial-based form of the drug, the supply has stabilized and the price has become affordable.

“The construction of the artemisinin-producing yeast required $25 million in funding and 150 person-years of work, typical of similar-sized bioengineering projects,” Keasling says. “New synthetic biology and computational technologies are needed to accelerate the development of productive biological systems and  reduce their costs, and industry needs access to them if traditional manufacturing is to be transformed by biomanufacturing.”

“Within the first five years of BOB, if it is fully funded by DARPA and corporate users, we will aim to speed the design time for developing desired biological systems so that it will be 50 times faster than it is today,” Maxon says. “We’ll also aim to make construction time five times faster than it is now and reduce costs by a factor of 20. The goal is to generate 350 molecules that currently can’t be manufactured with biological methods, including some that currently rely on petroleum sources and traditional manufacturing.”

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New DNA-editing technology spawns bold UC initiative

$10M gift will support the UC Berkeley, UCSF effort.

Jennifer Doudna, UC Berkeley

The University of California, Berkeley, and UC San Francisco are launching the Innovative Genomics Initiative (IGI) to lead a revolution in genetic engineering based on a new technology already generating novel strategies for gene therapy and the genetic study of disease.

The Li Ka Shing Foundation has provided a $10 million gift to support the initiative, establishing the Li Ka Shing Center for Genomic Engineering and an affiliated faculty chair at UC Berkeley. The two universities also will provide $2 million in startup funds.

At the core of the initiative is a revolutionary technology discovered two years ago at UC Berkeley by Jennifer A. Doudna, executive director of the initiative and the new faculty chair. The technology, precision “DNA scissors” referred to as CRISPR/Cas9, has exploded in popularity since it was first published in June 2012 and is at the heart of at least three start-ups and several heavily-attended international meetings. Scientists have referred to it as the “holy grail” of genetic engineering and a “jaw-dropping” breakthrough in the fight against genetic disease. In honor of her discovery and earlier work on RNA, Doudna received last month the Lurie Prize of the Foundation for the National Institutes of Health.

“Professor Doudna’s breakthrough discovery in genomic editing is leading us into a new era of possibilities that we could have never before imagined,” said Li Ka-shing, chairman of the Li Ka Shing Foundation. “It is a great privilege for my foundation to engage with two world-class public institutions to launch the Innovative Genomics Initiative in this quest for the holy grail to fight genetic diseases.”

In the 18 months since the discovery of this technology was announced, more than 125 papers have been published based on the technique. Worldwide, researchers are using Cas9 to investigate the genetic roots of problems as diverse as sickle cell anemia, diabetes, cystic fibrosis, AIDS and depression in hopes of finding new drug targets. Others are adapting the technology to re-engineer yeast to produce biofuels and wheat to resist pests and drought.

“We now have a very easy, very fast and very efficient technique for rewriting the genome, which allows us to do experiments that have been impossible before,” said Doudna, a professor of molecular and cell biology in the California Institute for Quantitative Biosciences (QB3) and an investigator in the Howard Hughes Medical Institute at UC Berkeley. “We are grateful to Mr. Li Ka-shing for his support of our initiative, which will propel ground-breaking advances in genomic engineering.”

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Crispr goes global

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How an entrepreneurial engineering education nurtured a biotech startup

UC San Diego alum Michael Benchimol is working to make chemotherapy more effective.

Michael Benchimol

Identify a real-world problem. Engineer a solution. And, if the solution works, figure out how it can be commercially viable. That’s what Michael Benchimol said he learned over seven years of working in the laboratory of Sadik Esener, a professor in the departments of nanoengineering and electrical and computer engineering at the University of California, San Diego. In Benchimol’s (Ph.D., electrical engineering, ’12) case, it specifically means building a company to advance a targeted drug delivery platform that could make chemotherapy more effective and less toxic to the healthy tissue in the body.

“I like to build things. That’s the engineering side of me,” said Benchimol, who also earned a master’s in electrical engineering at UC San Diego in 2008. “Creating a company was just a different form of creating something from nothing. I always had that interest and I saw that there was an opportunity here.”

The opportunity is a method of delivering chemotherapy drugs directly to cancerous tumors in the body, a longtime goal of next-generation cancer therapy research due to the toxic effects the drugs can have on the rest of the body. The field is enjoying a research heyday in part thanks to advances specifically in the area of nanotechnology. Benchimol says nanotechnology is enabling cancer researchers to leverage the best properties of cancer drugs and biocompatible materials, in a single therapy that can circulate undetected by the body’s immune system.

His company, Sonrgy, recently entered an exclusive licensing agreement with UC San Diego to further develop the company’s technology, which resulted from his Ph.D. and postdoctoral research at the Jacobs School of Engineering and UCSD Moores Cancer Center, where Esener, also directs the NanoTumor Center. Benchimol’s solution is unique in that it doesn’t rely on “tumor receptors” that the nanoparticle can seek out and “stick to” before releasing the drug. Rather, the Sonrgy platform, called SonRx, uses nanocarriers smaller than human cells that carry chemotherapy drugs through the body where they can be released at the tumor site by a doctor deploying ultrasound. The technology is in the preclinical stage.

“The SonRx technology addresses longstanding challenges related to stability and controlled release in nano-scale drug delivery,” said Michael Benchimol, who is Sonrgy’s chief technology officer, in a company statement about the licensing agreement.

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Puzzling quesiton in bacterial immune system answered

Berkeley researchers uncover the key to self-awareness in genome editor.

Short DNA sequences known as “PAM” (shown in yellow) enable the bacterial enzyme Cas9 to identify and degrade foreign DNA, as well as induce site-specific genetic changes in animal and plant cells. The presence of PAM is also required to activate the Cas9 enzyme. (Illustration by KC Roeyer.)

Short DNA sequences known as “PAM” (shown in yellow) enable the bacterial enzyme Cas9 to identify and degrade foreign DNA, as well as induce site-specific genetic changes in animal and plant cells. The presence of PAM is also required to activate the Cas9 enzyme.

A central question has been answered regarding a protein that plays an essential role in the bacterial immune system and is fast becoming a valuable tool for genetic engineering. A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley have determined how the bacterial enzyme known as Cas9, guided by RNA, is able to identify and degrade foreign DNA during viral infections, as well as induce site-specific genetic changes in animal and plant cells. Through a combination of single-molecule imaging and bulk biochemical experiments, the research team has shown that the genome-editing ability of Cas9 is made possible by the presence of short DNA sequences known as “PAM,” for protospacer adjacent motif.

“Our results reveal two major functions of the PAM that explain why it is so critical to the ability of Cas9 to target and cleave DNA sequences matching the guide RNA,” says Jennifer Doudna, the biochemist who led this study. “The presence of the PAM adjacent to target sites in foreign DNA and its absence from those targets in the host genome enables Cas9 to precisely discriminate between non-self DNA that must be degraded and self DNA that may be almost identical. The presence of the PAM is also required to activate the Cas9 enzyme.”

With genetically engineered microorganisms, such as bacteria and fungi, playing an increasing role in the green chemistry production of valuable chemical products including therapeutic drugs, advanced biofuels and biodegradable plastics from renewables, Cas9 is emerging as an important genome-editing tool for practitioners of synthetic biology.

“Understanding how Cas9 is able to locate specific 20-base-pair target sequences within genomes that are millions to billions of base pairs long may enable improvements to gene targeting and genome editing efforts in bacteria and other types of cells,” says Doudna who holds joint appointments with Berkeley Lab’s Physical Biosciences Division and UC Berkeley’s Department of Molecular and Cell Biology and Department of Chemistry, and is also an investigator with the Howard Hughes Medical Institute (HHMI).

Doudna is one of two corresponding authors of a paper describing this research in the journal Nature. The paper is titled “DNA interrogation by the CRISPR RNA-guided endonuclease Cas9.” The other corresponding author is Eric Greene of Columbia University. Co-authoring this paper were Samuel Sternberg, Sy Redding and Martin Jinek.

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UCSF, Quest Diagnostics launch collaboration to advance precision medicine

Areas of focus will include autism, oncology, neurology and women’s health.

June Lee, UC San Francisco

June Lee, UC San Francisco

UC San Francisco and Quest Diagnostics, the world’s leading provider of diagnostic information services, have formed a collaboration to accelerate the translation of biomedical research into advanced diagnostics in the field of precision medicine, for improved patient care, treatment and outcomes.

Initial clinical areas of focus include autism, oncology, neurology and women’s health.

The collaboration, which combines the research discoveries and capabilities of UCSF with the national testing database and technical and clinical development capability of Quest Diagnostics, has an overarching aim of enabling holistic and integrated diagnostic solutions that close gaps in care or enable new clinical value.

Under the terms of the agreement, scientists will jointly research, develop and validate diagnostic innovations to solve specific clinical problems and provide actionable information to improve patient care. The organizations will focus on diagnostics to advance precision medicine, an emerging field of medical science that aims to integrate the most informative data from molecular, clinical, population and other research to create predictive, preventive and precise medical solutions for patients. Quest Diagnostics would independently develop and validate any lab-developed tests for clinical use that emerge from the collaboration’s research.

Researchers will utilize laboratory-based diagnostics, imaging procedures and population analysis based on Quest’s national Health Trends database, the largest private clinical database in the U.S., based on more than 1.5 billion patient encounters, to advance precision medicine.

The alliance is the first master agreement that UCSF’s Office of Innovation, Technology and Alliances has signed with a clinical laboratory testing company and augments the university’s efforts to translate laboratory research into new therapies. The broad agreement lays the groundwork for multiple projects between the two organizations.

“Advances in technology and science have identified many promising opportunities to improve outcomes through insights revealed by novel diagnostic solutions, yet fulfilling the full potential of these opportunities often hinges on translational clinical studies which validate their value,” said Jay Wohlgemuth, M.D., senior vice president, science and innovation, Quest Diagnostics. “This unique collaboration between UCSF and Quest brings together the finest researchers and clinicians in the country to accelerate the development of a ‘product pipeline’ of scientific discoveries as clinically valuable diagnostic solutions that enable precision medicine for improved outcomes.”

The collaboration is launching with two specific projects already under way. One project involves Quest’s national database of molecular testing data to facilitate participation in research and development efforts related to genetic variations of autism, based on Quest’s CGH microarray ClariSure technology, which can help identify genetic mutations associated with autism and other developmental disorders. While there currently is no treatment for autism, a test that aids its diagnosis could help identify individuals who might be appropriate candidates for research studies that could lead to future therapies.

The second project aims to identify biomarkers to determine which children with glioma brain tumors may benefit from a drug that is currently available to treat the disease. That project will integrate molecular biomarker testing with advanced MRI imaging technologies. This project is the first phase of larger collaborative studies to develop and validate integrated care pathways, which would include laboratory diagnostics, imaging data and other clinical information to be used in the management of patients with brain cancer and neurological diseases.

UCSF has been at the forefront of the movement toward precision medicine, for which UCSF Chancellor Susan Desmond-Hellmann, M.D., M.P.H., co-authored the initial National Academy of Sciences paper that defined the new field. That paper set the vision of harnessing the vast amounts of genetic, environmental and health data worldwide to make health care more predictive, precise and targeted.

“There are many diagnostics projects underway at UCSF for which Quest could partner and contribute a great deal of value in turning an isolated research project into a diagnostic service or other technology that directly benefits patients,” said June Lee, M.D., F.A.C.C.P., director of early translational research at the UCSF Clinical and Translational Science Institute, which initiated the collaboration with Quest after several scientists from both organizations had formed isolated, but successful, research collaborations. “This agreement will give UCSF researchers access to Quest expertise in developing diagnostics, as well as in understanding the market conditions for projects on campus.”

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Schekman receives Nobel Medal in Stockholm ceremony

UC’s 13th Nobel laureate in medicine calls for more support of basic research.

Newly minted Nobel laureate Randy Schekman used his Nobel acceptance speech Dec. 10 in Stockholm to encourage more support for basic research, the “freedom of inquiry (that) nourished the careers of today’s laureates,” he said.

Schekman, a UC Berkeley professor of molecular and cell biology, delivered his brief remarks at the lavish Nobel banquet as he accepted the 2013 Nobel Prize in Medicine or Physiology on behalf of his two co-winners: Thomas Südhof of Stanford University and James Rothman of Yale University.

Since the prize was announced Oct. 7, Schekman has used the spotlight to push for increased funding of basic research – the wellspring of his own seminal discoveries in yeast – and of public universities, which were underrepresented in this year’s American Nobel lineup. Of the nine American Nobelists, Schekman was the only one from a public institution.

“I wish particularly to acknowledge the Nobel Foundation for its recognition of basic science,” he said. “This year’s laureates in the natural sciences reflect the value of curiosity-driven inquiry, unfettered by top-down management of goals and methods.”

Schekman was referring to the increasing desire of U.S. funding agencies “to want to manage discovery with expansive so-called strategic science initiatives at the expense of the individual creative exercise we celebrate today.”

The banquet was the crowning event of a weeklong series of celebrations honoring the new Nobelists, during which Schekman delivered a lengthier speech on Dec. 7 about his research on yeast secretion. This work, which Schekman pursued purely out of curiousity, turned out to be critical to the success of the biotechnology industry.

Schekman traveled to Stockholm with his wife, Nancy Walls, their son and daughter and his father. During his banquet acceptance speech, he expressed appreciation for a broad range of friends and colleagues.

“I view this occasion as one of the great moments of my life, one that I am thrilled to share with my wife and children, my father, and family, friends, colleagues and the students of mine who made this day possible,” he said.

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Single-cell genome sequencing gets better

New approach exhibits comparatively little “amplification bias.”

Jeff Gole

Jeff Gole worked on this project as a Ph.D. student at UC San Diego.

Researchers led by bioengineers at UC San Diego have generated the most complete genome sequences from single E. coli cells and individual neurons from the human brain. The breakthrough comes from a new single-cell genome sequencing technique that confines genome amplification to fluid-filled wells with a volume of just 12 nanoliters.

The study was published in the journal Nature Biotechnology on Nov. 10. An animated video describing the new approach, which is called the Microwell Displacement Amplification System or MIDAS, is available here.

“Our preliminary data suggest that individual neurons from the same brain have different genetic compositions. This is a relatively new idea, and our approach will enable researchers to look at genomic differences between single cells with much finer detail,” said Kun Zhang, a professor in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering and the corresponding author on the paper.

The researchers report that the genome sequences of single cells generated using the new approach exhibited comparatively little “amplification bias,” which has been the most significant technological obstacle facing single-cell genome sequencing in the past decade. This bias refers to the fact that the amplification step is uneven, with different regions of a genome being copied different numbers of times. This imbalance complicates many downstream genomic analyses, including assembly of genomes from scratch and identifying DNA content variations among cells from the same individual.

Sequencing the genomes of single cells is of great interest to researchers working in many different fields. For example, probing the genetic make-up of individual cells would help researchers identify and understand a wide range of organisms that cannot be easily grown in the lab from the bacteria that live within our digestive tracts and on our skin, to the microscopic organisms that live in ocean water. Single-cell genetic studies are also being used to study cancer cells, stem cells and the human brain, which is made up of cells that increasingly appear to have significant genomic diversity.

“We now have the wonderful opportunity to take a higher-resolution look at genomes within single cells, extending our understanding of genomic mosaicism within the brain to the level of DNA sequence, which here revealed new somatic changes to the neuronal genome. This could provide new insights into the normal as well as abnormal brain, such as occurs in Alzheimer’s and Parkinson’s disease or schizophrenia,” said Jerold Chun, a co-author and professor in the Dorris Neuroscience Center at The Scripps Research Institute.

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