TAG: "Biotechnology"

New electron beam writer enables next-gen biomedical technology

Technology allows researchers to precisely write very small patterns on large substrates.

Ryan Anderson, a process engineer for the Nano3 facility in the Qualcomm Institute, prepares to remove a sample from the Vistec EBPG5200 electron beam writer.

Ryan Anderson, a process engineer for the Nano3 facility in the Qualcomm Institute, prepares to remove a sample from the Vistec EBPG5200 electron beam writer.

The new electron beam writer housed in the Nano3 cleanroom facility at the Qualcomm Institute is important for electrical engineering professor Shadi Dayeh’s two major areas of research. He is developing next-generation, nanoscale transistors for integrated electronics; and he is developing neural probes that have the capacity to extract electrical signals from individual brain cells and transmit the information to a prosthetic device or computer. Achieving this level of signal extraction or manipulation requires tiny sensors spaced very closely together for the highest resolution and signal acquisition. Enter the new electron beam writer.

Electron beam (e-beam) lithography enables researchers to write very small patterns on large substrates with a high level of precision. It is a widely used tool in information technology and life science. Applications range from writing patterns on silicon and compound semiconductor chips for electronic device and materials research to genome sequencing platforms. But the ability to write patterns on the scale afforded by the Nano3 facility — with its minimum feature size of less than 8 nanometers on wafers with diameters that can be as large as 8 inches — is unique in Southern California. Before the facility opened earlier this year, the closest comparable e-beam writer was in Los Angeles. In an e-beam writer, unique patterns are “written” on a silicon wafer coated with a polymer resist layer that is sensitive to electron irradiation. The machine directs a narrowly focused electron beam onto the surface marking the pattern, making parts of the resist coating insoluble and others soluble. The soluble area is later washed away, revealing the pattern which can have sub-10 nanometer feature dimensions.

Bioengineering professor Todd Coleman will use the new e-beam writer as one essential step in the building of his epidermal, or tattoo, electronic devices. The devices are designed to acquire brain signals for a variety of medical applications, from monitoring infants for seizures in neonatal intensive care to studying the cognitive impairment associated with Alzheimer’s disease or dementia, and soldiers struggling with post-traumatic stress syndrome.

Electrical engineering Ph.D. candidate Andrew Grieco is using the machine to develop a new type of optical waveguide that promises to improve efficiency and reduce power consumption. Grieco works in the laboratory of Shaya Fainman, professor and chair, Department of Electrical and Computer Engineering. Developing on-chip optical networking devices such as waveguides, switches and amplifiers is a critical step in the development of optical chips. Although information systems rely primarily on fiber-optic networks to connect and share data around the world, the underlying computer technology is still based on electronic chips, causing data traffic jams.

“Any local company that has an investment in nanoscale science and technology should greatly benefit from this machine. It’s a powerful tool that is hard to find in a typical university setting or within local industry,” said Dayeh (Ph.D., 2008 UC San Diego), who joined the faculty in 2012. “It’s a unique tool that is being brought to San Diego.“

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The story behind the anthrax killer

Under the sea, UC San Diego researchers find promising sources to treat human diseases.

Chris Kauffman, a staff research associate at UC San Diego's Scripps Institution of Oceanography, collects samples for biomedical research off Madiera Island.

Chris Kauffman, a staff research associate at UC San Diego's Scripps Institution of Oceanography, collects samples for biomedical research off Madiera Island.

William Fenical made headlines in July when he announced a promising new candidate in the search for novel sources to treat human diseases, the latest in his long and storied biomedical research career at Scripps Institution of Oceanography at UC San Diego.

This time, Fenical identified a new compound from the ocean that effectively kills anthrax, the feared biological weapon, as well as methicillin-resistant Staphylococcus aureus, or MRSA, the bacteria that has proliferated in recent years and proven problematic to treat. Fenical and his colleagues called the new compound “anthracimycin,” and hold hope that one day it will lead to the development of a powerful new drug.

“The real importance of this work is the fact that anthracimycin has a new and unique chemical structure,” said Fenical, a distinguished professor of oceanography and pharmaceutical science at Scripps “The discovery of truly new antibiotic compounds is quite rare. This discovery adds to many previous discoveries that show that marine bacteria are genetically and chemically unique.”

Fenical is quick to share credit for the discovery with a team of researchers in his laboratory. In this case special attention goes to Chris Kauffman, a staff research associate who has been part of Fenical’s team since 1991.

In the depths of Fenical’s research labs, Kauffman operates the group’s fermentation facility, a crucial area for teasing out promising compound candidates from the mind-boggling diversity of chemical structures found in the world’s vast oceans.

Kauffman also has emerged as the group’s field expedition leader in their search near and far for novel materials from the sea. He has logged more than 450 research dives to locations as close as La Jolla and as far as Fiji, Papua New Guinea, Palau, the Philippines, and the Red Sea.

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Scientists devise innovative method to profile, predict behavior of proteins

New technique lets researchers pinpoint, map thousands of enzyme interactions.

Nevan Krogan

Nevan Krogan

An enzyme is a tiny, well-oiled machine.

A class of proteins that are made up of multiple, interlocking molecular components, enzymes perform a variety of tasks inside each cell. However, precisely how these components work together to complete these tasks has long eluded scientists.

But now, a team of researchers has found a way to map an enzyme’s underlying molecular machinery, revealing patterns that could allow them to predict how an enzyme behaves – and what happens when this process disrupted.

In the latest issue of the journal Cell, a team of scientists led by Gladstone Institutes and UC San Francisco investigator Nevan Krogan, Ph.D., Texas A&M University’s Craig Kaplan, Ph.D., and UCSF professor Christine Guthrie, Ph.D., describe a new technique – called the point mutant E-MAP (pE-MAP) approach – that gives researchers the ability to pinpoint and map thousands of interactions between each of an enzyme’s many moving parts.

The researchers focused on a well-known enzyme – called RNA polymerase II (RNAPII) – and used the single-cellular yeast species S. cerevisiae as a model. Researchers had previously mapped the physical structure of RNAPII, but not how various parts of the enzyme work with other proteins within the cell to perform vital functions.

“Scientists know RNAPII’s physical structure, but this large enzyme has many distinct regions that each perform distinct functions,” said Kaplan, who is also a scientist at Texas A&M AgriLife. “We wanted to connect the dots between these regions and their function.”

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Acclaimed molecular biologist named new QB3-UCSF director

Nevan Krogan to set ambitious scientific course for UCSF site.

Nevan Krogan

Nevan Krogan

UC San Francisco has tapped Nevan Krogan, Ph.D., to lead the UCSF site of the California Institute for Quantitative Biosciences (QB3), known as QB3-UCSF.

Krogan, a professor of cellular and molecular pharmacology and an investigator at the J. David Gladstone Institutes who came to UCSF in 2006 as a Sandler Fellow, is known for his prolific research into developing and using systems biology approaches to help understand complex biological phenomenon.

In his new role, which began in July, Krogan will help enable the research of UCSF investigators directly affiliated with QB3, and bring approaches and technologies from the physical and quantitative sciences and engineering within reach of the entire UCSF community. He will report to UCSF Vice Chancellor for Research Keith Yamamoto, Ph.D., and Regis Kelly, Ph.D., director of the entire QB3 consortium, while working in conjunction with faculty and trainees at QB3’s three campuses: UCSF, UC Berkeley and UC Santa Cruz.

“Promoting collaboration is absolutely critical in this role, and there are few scientists more collaborative than Nevan,” Yamamoto said. “In following the excellent efforts of the previous director, Brian Shoichet, Nevan has laid out an exciting and ambitious scientific agenda to develop and exploit new experimental and computational technologies to identify and understand the components of the governing circuitry, the logic systems, within and between cells.”

QB3 was founded in 2000 by former Gov. Gray Davis as one of four California Institutes for Science and Innovation that would support UC science and help translate it into economic activity and public benefit for the state of California. QB3, which now has 238 affiliated faculty members on three campuses, is the only institute focused on the quantitative biosciences. At UCSF, headquarters for QB3, 84 faculty are affiliates from the schools of medicine and pharmacy.

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100K Genome Project unveils 20 more foodborne pathogen genomes

Project aims to sequence the genomes of 100,000 bacterial and viral genomes.

This genome sequencing effort is focused on speeding the diagnosis and treatment of foodborne diseases. The 100K Genome Project, led by UC Davis, the U.S. Food and Drug Administration’s Center for Food Safety and Applied Nutrition, and Agilent Technologies, today (July 22) announced that it has added 20 newly completed genome sequences of foodborne disease-causing microorganisms to its public database at the National Center for Biotechnology Information.

The genomes were determined using Single Molecule, Real-Time (SMRT) Sequencing technology from Pacific Biosciences of California Inc.

This brings to 30 the number of genomic sequences completed by the 100K Genome Project, which aims to sequence the genomes of 100,000 bacterial and viral genomes. This genome sequencing effort is focused on speeding the diagnosis and treatment of foodborne diseases, as well as shortening the duration and limiting the spread of foodborne illness outbreaks. In the United States alone, foodborne diseases annually sicken around 48 million people and kill approximately 3,000, according to the Centers for Disease Control and Prevention.

The newly deposited sequences include several isolates of Salmonella, Listeria, Campylobacter and Vibrio, as well as a full characterization of their epigenomes – a diagnostic feature that defines how the DNA is chemically modified and changes how the organism behaves.

“These finished genome sequences represent the highest quality standard, with each strain closed in a single bacterial chromosome and the associated mobile DNA,” said Bart Weimer, director of the 100K Genome Project and professor at the school of veterinary medicine at UC Davis.  “They also contain complete associated phage or plasmid elements, which are critical for understanding pathogenicity, drug resistance and other biologically important traits that are linked to survival.

“The genomes we have analyzed to date are from pathogens responsible for common and debilitating foodborne infections,” Weimer said, noting that the ready availability of this information will aid in reducing the time needed to diagnose and define outbreak strains.

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UCSF to host life science tech transfer summit

Event will be July 29-30.

Erik Lium, UC San Francisco

An international conference focusing on life science technology transfer will take place in late July at UC San Francisco’s Mission Bay campus. The 2013 Tech Transfer Summit (TTS), North America will run from July 29 to 30, focusing on early stage tech transfer, licensing, partnering and investment.

The conference is organized by TTS Ltd. and UCSF’s Office of Innovation, Technology & Alliances (ITA), which oversees technology transfers, entrepreneurship and innovative research alliances with bioscience commercial, nonprofit and government organizations. ITA is serving as the host partner, and BayBio and QB3 are also providing support for the event, whose speakers and attendees include a broad range of stakeholders in the life sciences and health care industries.

“UCSF is pleased to host the Tech Transfer Summit as part of our commitment to partnering with industry, government, private nonprofit and peer organizations to advance health worldwide, directly benefiting patients,” said ITA Assistant Vice Chancellor Erik Lium, Ph.D. Lium pointed to UCSF’s newly created Center for Digital Health Innovation (CDHI) as an example of the university’s focus on leading revolutions in health.

Early bird registration discounts are available through June 30. Registration and fee information is available at techtransfersummit.com/northamerica2013/registration. For more information, email terry.graham@ucsf.edu.



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Onyx Pharmaceuticals, UCSF announce Oncology Innovation Alliance

Strategic alliance focused on advancing drug discovery and development.

Jeffrey Bluestone, UC San Francisco

Onyx Pharmaceuticals Inc. (Nasdaq: ONXX) and the UC San Francisco Helen Diller Family Comprehensive Cancer Center today (June 3) announced the formation of the Oncology Innovation Alliance (OIA), a public-private partnership focusing on the discovery and development of novel therapies and their potential role in treating various types of hematologic cancers and solid tumors.

“This collaboration will leverage expertise across UCSF and Onyx to further our collective understanding of cancer and hopefully translate scientific research rapidly from the laboratory to the clinic and, ultimately, to patients,” said Pablo J. Cagnoni, M.D., executive vice president, global research & development and technical operations at Onyx Pharmaceuticals. “The UCSF Helen Diller Family Comprehensive Cancer Center is a recognized leader in oncology research and patient care, and Onyx is committed to forming strategic alliances that encourage innovation and the advancement of new treatments for patients.”

The alliance aims to transform cancer care by harnessing the expertise in fundamental science and medicine at both UCSF and Onyx to address the full continuum of that care, from prediction and diagnosis to new therapies and post-treatment monitoring, to identify opportunities to improve the patient experience and outcomes.

The partnership will focus on drug discovery and development, and seeks to advance the broader scope of patient care while contributing to the biological understanding of hematologic malignancies and solid tumors, discovering novel drug targets, identifying potential biomarkers to support patient selection and implementing innovative clinical development approaches.

“UCSF and Onyx share a vision of transforming care for patients with cancer, so we can precisely diagnose, treat and possibly even prevent cancer from occurring,” said Jeffrey Bluestone, Ph.D., executive vice chancellor and provost at UCSF. “Our goal is to create an umbrella partnership that enables us to work together to better understand the cascade of events within a cell that leads to disease, and find innovative ways to use that knowledge to diagnose and treat patients far more precisely than we can today.”

A joint steering committee comprised of representatives from Onyx and UCSF will provide oversight of the alliance. The term of the agreement extends for three years. Financial terms of the collaboration were not disclosed.

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Researchers find synthetic compound effective in anti-obesity study

Originally developed from sun anemone venom, ShK-186 boosts metabolism, UC Irvine scientists find.

George Chandy, UC Irvine

Scientists at UC Irvine have discovered that a synthetic compound originally derived from a sun anemone toxin enhances metabolic activity and shows potential as a treatment for obesity and insulin resistance.

The findings, published online this week in Proceedings of the National Academy of Sciences, present the first evidence that the drug candidate – which in March got positive results in a phase-one safety clinical trial – may work in an anti-obesity capacity.

UC Irvine licensed ShK-186 to Kineta Inc., a Seattle-based biotechnology company, in 2009; it’s the company’s lead drug candidate. Kineta is developing the compound to treat autoimmune diseases, such as multiple sclerosis, psoriatic arthritis and lupus. It has also licensed ShK-186 for the treatment of metabolic syndrome and obesity.

Potassium channels regulate cell membrane activities and control a variety of other cellular processes. ShK-186 selectively blocks the activity of a protein that promotes inflammation through the Kv1.3 potassium channel. Earlier research using mice without a Kv1.3 potassium channel gene suggested that Kv1.3 may regulate body weight and the basal metabolic rate.

In the current study, Dr. George Chandy and colleagues evaluated ShK-186 in tests on obese mice that ate a high-fat, high-sugar diet. They found that the therapy reduced weight, white fat deposits, liver fat, blood cholesterol and blood sugar by activating calorie-burning brown fat, suppressing inflammation of white fat and augmenting liver function. The compound had no effect on mice that ate standard chow.

“This is a new twist in a sustained journey of discovery made over 30 years that charts the course for expeditious translation to humans who suffer from potentially lethal consequences of metabolic syndrome and autoimmune diseases,” said Chandy, a UC Irvine professor of physiology & biophysics and a Kineta scientific adviser.

“Knowing that ShK-186’s unique mechanism of action may have broad applications across multiple therapeutic disciplines, such as autoimmune diseases and now obesity, further adds to the potential of this compound. This study also shows how medical progress can be made through academic and private-sector partnerships,” added Charles Magness, president and CEO of Kineta.

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New center targets ocean contaminants and human health

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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Nanodiamonds could improve effectiveness of breast cancer treatment

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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International consortium builds ‘Google map’ of human metabolism

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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Cheap, easy technique to snip DNA could revolutionize gene therapy

“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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