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Biotech / Medical : Celera Genomics (CRA) -- Ignore unavailable to you. Want to Upgrade?

To: gao seng who wrote (367)	5/13/2000 10:48:00 PM
From: gao seng	Read Replies (1) \| Respond to of 746

NIH Freezing out non-participants? STRUCTURAL GENOMICS: Protein Data Justice for All Robert F. Service* Scientists who crack protein structures and colleagues who want to decipher what these proteins do are on the verge of a watershed agreement that would usher structural biology into the genomic era. The carefully crafted guidelines are designed to help coordinate international financing of publicly funded protein structure efforts and ensure prompt release of structure data so that no team has an unfair advantage in working out the functions of unknown proteins. The guidelines, being finalized as Science went to press, come at a time when robotics and computer automation promise to transform structural biology into a high-speed effort, dubbed "structural genomics," in which researchers will churn out thousands of protein structures in the next 5 years. Nurturing this souped-up approach, the National Institutes of Health (NIH) this fall plans to fund up to six structural genomics pilot centers to establish and test techniques for high-throughput x-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, the workhorse technologies of structural biology. Similar approaches are being adopted or considered in Japan, the United Kingdom, France, Brazil, and Germany (Science, 17 March, p. 1954). To help coordinate these efforts, officials at NIH and Britain's Wellcome Trust last month brought some 50 leading protein specialists to the Wellcome Trust Genome Campus in Cambridge, U.K., for a brainstorming session on how to release data quickly and fairly. They had a gulf to bridge. "Bioinformatics experts want fast access" so they can run follow-up experiments, says John Norvell, who heads the structural genomics program at the National Institute of General Medical Sciences in Bethesda, Maryland. But "experimentalists want time to check the data." The issue boils down to how protein structures are gleaned and checked before release, says Wayne Hendrickson, a structural biologist at Columbia University. Computer programs, fed data from x-ray crystallography and NMR experiments, generate the likeliest set of three-dimensional coordinates for all of a protein's atoms. Bioinformatics experts initially wanted guidelines that mandate the release of those computer predictions the instant they are produced. Such a policy would be similar to the way sequence data from the publicly funded human genome project are posted daily on the Web. "That did not fly," says Tom Terwilliger, an x-ray crystallographer at Los Alamos National Laboratory in New Mexico. Experimentalists maintain that protein structure analysis is more complex than spitting out raw genome sequence data. Each modeling prediction must be vetted, Hendrickson says. Several participants, he says, felt there's "no need to abandon the current standards of investigators making the decision" on when data are ripe for release. But although structural biologists will still make the call on when data are solid, they won't be allowed to withhold a structure for the sake of determining its function. That means changing the status quo. When a protein structure is submitted to a journal today, Hendrickson says, it's almost always accompanied by findings--from experiments that alter key amino acids in the protein, for instance--that allow scientists to make educated guesses about how the protein works. But with a high-speed approach to solving protein structures, says Norvell, "publishing will have to be done in a different way." NIH and other agencies that plan to pour money into the structural genomics centers don't want to freeze out biologists not associated with the centers. According to Hendrickson, "everyone agreed that the concept should not give those groups a privileged status." As a compromise, researchers will be asked to publish their results--most likely in electronic format or as a brief summary in a specialist journal--within 2 to 4 weeks of finishing a structure, says Stephen Burley, a structural biologist at The Rockefeller University in New York City. "The moment the paper is posted on the Web," he says, "the coordinates would be placed in the Protein Data Bank," which is freely available to all researchers. The burden will be primarily on funders to enforce the timelines. They're accustomed to that, Burley says: Agencies regularly use their leverage over purse strings to ensure that structural biologists submit coordinates to the Protein Data Bank as soon as findings are published. As an additional prod, structural biologists plan to add a little peer pressure. Hendrickson and others say the new guidelines call on each structural genomics center to keep a log on the Web of which structures they are attempting to solve. They would chart milestones such as cloning, isolating, and purifying a protein, and coaxing it to form a crystal. This will not only help to prevent several groups from working on the same projects, says Hendrickson, but "it will put internal pressure on the groups that they wouldn't be able to hold something forever." -------------------------------------------------------------------------------- With reporting by Michael Hagmann in Cambridge, U.K.