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BY DAWN LEVY Fighting blindness with digital camera technology. Trapping pollutants instead of removing them. Educating scientists and engineers in medicine so patients can benefit. These were some of the projects described by the first round of Bio-X grant recipients at a March 1 symposium. And round two is coming up. "Because of the efforts of [Bio-X Scientific Leadership Council Chairman] Matt Scott and our president, John Hennessy, we were able to now offer again this interdisciplinary initiative program to our faculty," announced Professor Harvey Cohen, Bio-X Interdisciplinary Initiatives Committee chair. Stanford faculty recently were e-mailed a request for letters of intent, due May 1. "We want the initiatives to come from our faculty, and thereby have the faculty directly involved in determining the nature of Bio-X." The first grant recipient to speak was Axel Brunger, Molecular and Cellular Physiology, who aims to automate determination of protein structures with co-investigators Leonidas Guibas, Jean-Claude Latombe and Daniel Russel (Computer Science), Jun Aishima (Stanford Synchrotron Radiation Laboratory and Lawrence Berkeley National Laboratory) and Paul Adams (University of California-Berkeley). While the process of determining gene sequences is highly automated, the process of determining the 3-D structures of the proteins encoded by those genes is done almost entirely by hand by chemists using interactive graphics displays. The project uses computers to analyze shapes of proteins, which will speed determination of their structures and functions. And that will help scientists design drugs that interact with targets for maximal effect but minimal side effects. Jane Parnes, Immunology and Rheumatology, presented a cross-disciplinary curriculum to teach graduate students in biological sciences and engineering more about medicine. She developed and evaluated a course on diabetes with Elizabeth Mellins (Pediatrics), Decker Walker (School of Education) and Larry Leifer (Mechanical Engineering, Stanford Learning Lab). "There's been an enormous burst of information about a molecular and cellular basis for disease, as well as increasing advances in engineering technologies," Parnes said. "However, there's still a gap between the acquisition of this knowledge and the application to human disease, both diagnosis and treatment." In lectures, students learned about disease complications, involvement of organ systems, sources of medical information and clinical decision-making. They visited a diabetes clinic, clinical laboratory and start-up company. For collaborative projects, one group developed a novel plan for early screening for type 2 diabetes. Another group proposed a cure for type 1 diabetes using transplantation of encapsulated islet cells from fish. A third group proposed an implanted device to control blood glucose with a glucose sensor linked to an insulin pump. Harvey Fishman, Ophthalmology, spoke of efforts to develop an "artificial synapse chip" with Stacey Bent (Chemical Engineering), David Bloom (Electrical Engineering) and Mark Blumenkranz (Ophthalmology). The goal is to treat blinding diseases of the retina, including age-related macular degeneration -- the leading cause of blindness in the United States among people over age 65, with about 130,000 new cases per year. "What's really interesting in macular degeneration is that the neurons are still intact," Fishman said. "The neurons are ready to receive signal; they're just not getting their signal. The biologic 'film' -- the photographic film of your eye -- is now damaged." Fishman's group aims to bypass injured cells by connecting digital video camera technology to individual retinal cells in patients' eyes. The researchers are adapting techniques developed by the computer chip industry to build an artificial nerve connection that will be fashioned from silicon and upon which the microcircuitry of retinal cells will be regrown. Richard Luthy, Civil and Environmental Engineering, is working with Stephen G. Monismith (Civil and Environmental Engineering), David Epel (Hopkins Marine Station) and Richard Zare (Chemistry) to minimize harm from contaminated sediments. Bottom dwellers can acquire toxins from sediments. Toxins bioaccumulate, or become more concentrated, as they pass up the food chain. The researchers are attempting to better understand sediment geochemistry that influences bioavailability and bioaccumulation of pollutants. They fed clams pollutants bound to sediments containing different sorbents and found that the animals' abilities to assimilate pollutants depended on binding properties of the sorbents. If sorbents could be added in the field to help sequester contaminants, it may be cheaper and safer to leave polluted sediments than to dredge them up and incinerate them. "The Bio-X Program has generated excitement and interest on the part of the Department of Defense, which has a lot of contaminated sites, and other industry groups as well," Luthy said. Dwight Nishimura, Electrical Engineering, is developing a microscopy system based on magnetic resonance (MR) technology with co-investigators Gerald Berry (Pathology), Bob Hu (Medicine) and Greg Kovacs and Calvin Quate (Electrical Engineering). They aim to design hardware for noninvasive imaging of biological tissues with a resolution of a few cells. Nishimura talked about the challenges of looking at smaller and smaller areas. Going from 10 microns down to 1 micron requires advanced hardware. "If you want to speculate on submicron resolution, then you're talking marketing or divine intervention," he said. Brian Kobilka, Molecular and Cellular Physiology, is using single-molecule spectroscopy to analyze the largest groups of targets for drug development -- G protein coupled receptors. These receptors are docking sites for important biomolecules including dopamine, adrenalin and seratonin. With Gadi Peleg and Richard Zare (Chemistry) and Pejman Ghanouni (Molecular and Cellular Physiology), he is trying to understand the mechanism by which an agent binding to the receptor on the cell surface changes the receptor's shape and transmits a signal to activate G protein inside the cell. Their data suggested the receptor undergoes a sequence of shape changes rather than an abrupt transition. Jean-Claude Latombe, Computer Science, is exploring molecular motion with co-investigators Douglas Brutlag (Biochemistry), Leonidas Guibas (Computer Science), Michael Levitt (Structural Biology) and Vijay Pande (Chemistry). Existing techniques for simulating molecular motions generate individual pathways. The Latombe group is exploring a "roadmap" of multiple pathways. The roadmap is generated by randomly sampling shapes that the molecule assumes. Each path in the roadmap represents a probability -- the likelihood that the molecule will follow this route. The researchers analyzed protein folding with this approach and found it much faster than current methods. Helen Bronte-Stewart, Neurology, is analyzing 3-D limb movement in dystonia, a condition characterized by involuntary movements, with co-investigators Christoph Bregler (Computer Science), Jean-Claude Latombe (Computer Science) and Eugene Alexander (Biomechanical Engineering). Their "pacemaker" for the brain provides electrical stimulation and restores normal movement to patients. Stephen Monismith, Civil and Environmental Engineering, studies how currents and turbulence influence the productivity of reef ecosystems with Gregory Shellenbarger (Civil and Environmental Engineering), Adina Paytan (Geologic and Environmental Sciences) and Amatzia Genin (Steinitz Marine Lab, Hebrew University). Usually coral reefs are biologically productive despite the fact that they tend to occur in otherwise unproductive regions -- a paradox originally noted by Darwin. Studies that the researchers conducted in the Red Sea indicate that reefs may be remarkably efficient at extracting what they need from the adjacent ocean. Jim Swartz, Chemical Engineering, is working to rapidly synthesize patient-specific vaccines to treat B-cell lymphoma, a cancerous disease of antibody-producing cells. Co-investigators include Ronald Levy, Shoshana Levy, Hendrik Veelken and Greg Kanter (Medicine) and Alexei Voloshin and Nathalie Michel-Rydellet (Chemical Engineering). "The concept is very simple, but it's also very profound," Swartz said. "It involves recruiting the patient's own immune system to attack this basic and very terrible disease." B cells produce one specific antibody protein that remains attached to the cell and provides a unique target for attack. But each patient needs a new and different vaccine. With conventional technology, new vaccines take months to produce. To produce vaccines faster and cheaper, the researchers are developing technology for cell-free protein synthesis. "We're using the same machinery that generates proteins in a living cell, but we're doing it in a test tube," Swartz said. "The Bio-X concept really works," Swartz said. "The
collaboration with Professor Levy's group has led us to do
something that we never could have done otherwise." SR |
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Stanford Report, March 20, 2002
