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The movie begins with three compartments, or vacuoles, docked like nanometer-sized flying saucers inside a yeast cell. The boundary membranes, which look like interior walls, are where the three vacuoles meet. Suddenly, they break loose, flapping inside the outer membrane in what has become a single organelle. This is membrane fusion—essential for transferring chemical information inside cells—and, until now, nobody knew how it happened. The previous model of a radially expanding pore was unexpectedly replaced by this mechanism called vertex ring fusion by its discoverers, William Wickner, Dartmouth Medical School biochemistry professor, and colleagues. Using time-lapse fluorescence microscopy, they demonstrated that boundary membrane is released from the vertices, or junctures of boundary and exterior membranes (L. Wang et al., "Vacuole fusion at a ring of vertex docking sites leave membrane fragments within the organelle," Cell, 108:357-69, Feb. 8, 2002). Nobody yet knows what happens to the released membrane after it enters the fused organelle's interior, Wickner notes. Although he likes the team's computerized movies, he is most excited about the colorimetric assay they devised that turns yellow when fusion occurs among purified vacuoles in vitro. "It's the key to whatever this method can contribute to further understanding." —Steve Bunk Watson waxes philosophical The inimitable James Dewey Watson stopped recently in Philadelphia while touting his new book, Genes, Girls and Gamow: After the Double Helix (New York: Alfred A. Knopf, 2002). Arthur Caplan, director of the University of Pennsylvania's Center for Bioethics, was present as well, but he had different plans for the nearly 75-year-old scientist, whom Caplan jokingly describes as "sometimes a bit inhibited." Caplan pressed Watson on some of today's hot bioethical topics, and how science has changed since Watson and Francis Crick published their work on the double helix. Regarding stem cells, Watson says, "The opposition is largely religious so the reasons I feel are largely irrational. Limiting the strains [as President George W. Bush has done] created something that sounds better than it is. It's another example of religion as a cause of trouble." He doesn't think human cloning should be banned. "They could make a law saying you can't make more than 20 copies of Meg Ryan—I'd agree with that." Cloning, he says, will probably be very hard, "and it won't happen in my lifetime. So, it's not worth worrying about." Regarding the controversy over who gets credit for discovering the helix first, he and Crick or fellow scientist Rosalind Franklin, he says, "There will never be an answer as to was this ethical or not." Though, he says, he and Crick had sufficient information to build the double helix without Franklin's data. "If all that gold is there and someone asks, do you want to find it, you say sure because if you get the gold you get the girls and all those other sorts of things that come with it." —Brendan A. Maher Researchers Mine Mouse for Olfactory Receptor Genes Reprinted with Permission from Nature NeuroscienceSequence logos for OR genes In a labor-intensive task that required combing the Celera Genomics Group mouse genome multiple times, researchers at Columbia University identified more than 95% of the olfactory receptor (OR) genes, the largest gene superfamily in vertebrates (X. Zhang, S. Firestein, "The olfactory receptor gene superfamily of the mouse," Nature Neuroscience, 5:124-33, 2002). Before, only about 300—and mostly partial—sequences were available. Now, with their work, molecular biologists Stuart Firestein and Xinmin Zhang have identified 1,296 genes in 27 clusters on every mouse chromosome except 12 and Y. "We can now go in and really explore these receptors and find out what their different structures mean," Firestein says. Some genes differ by a single amino acid, while others share similarities of 30%. About 20% of the ORs are nonfunctioning pseudogenes. Now that they are identified, it will be easier to clone the OR genes, Firestein says, which should open up research on their exact function. Some, but not all, OR genes are known to be active in olfaction, which occurs when odor molecules bind to ORs on the olfactory neuron's surface, are translated into nerve impulses and then interpreted in the brain as specific smells. Identifying the ORs is particularly important because they belong to the superfamily of G-protein coupled receptors (GPCRs), which are "arguably the most important class of receptors that we have," Firestein notes. He estimates that 50% of drugs currently in the pipeline or on the market target GPCRs. —Jennifer Fisher Wilson Planting a Virtual World Marlene J. ViolaLong Live the Gene British scientists hope that six virtual Genetic Knowledge Parks will encourage collaboration among academic institutions in six UK cities and regions. Researchers foresee conducting joint investigations and public education programs in Oxford, Cambridge, London, Newcastle, and Wales and the Northwest. "Up until now, there's been a competitive nature [among] the labs, but there will be an effort to see how we can collaborate," says Steve Humphries, director of the genetics application unit of the London knowledge park. "We'd like to be singing from the same song sheet." Additionally, new genetics reference laboratories in Salisbury and Manchester will specialize in creating new tests and technologies. Alan Milburn, the British Health Secretary, announced that the knowledge parks would "help prepare the National Health Service (NHS) for the genetics revolution." They will tackle projects ranging from familial hypercholestorolemia to breast cancer and smoking cessation. Crispin Kirkman, chief executive of the London-based BioIndustry Association, says the parks may help show physicians and the public the benefits of genetic testing and its applications. —Hal Cohen More Dollars for Molecule Design The W.M. Keck Foundation of Los Angeles recently awarded $1.8 million (US) to the Johns Hopkins University School of Medicine to create the W.M. Keck Center for Rational Design of Biologically Active Molecules. This is the group's third chemical genomics grant in about 14 months. Keck also awarded funding to support the design and application of synthetic molecules for biomedical research and training at Harvard University and the University of Wisconsin-Madison. "It was an odd coincidence where three requests for the same field came in at the same time," says Roxanne Ford, the foundation's program director, "But we saw this as a great opportunity to jump-start an exciting, new field." Chemical genomics, a useful way to unravel the proteome, includes disciplines such as synthetic chemistry, informatics, and genomics, and techniques such as high-throughput screening. As researchers discover new proteins, they are challenged to understand connections to larger biological processes and how they can be manipulated, says Rebecca Ward, director of research affairs at Harvard's Institute of Chemistry and Cell Biology. A payoff in drug discovery is at least five years away, Ford adds, but high-risk ventures are a Keck specialty. "It's difficult to know what and how important what we discover will be," says Laura Kiessling, professor of chemistry and biochemistry at the University of Wisconsin, Madison. "But it's become apparent that chemical genomics provides a much broader view of things other than proteins." —Hal Cohen Transcription Factors Could Get Redacted To the chagrin of many cash-poor students, the profitable reselling of their molecular biology textbooks may not be an option this year. Rockefeller University researchers James Darnell and Ali Brivanlou are proposing an ambitious reclassification of all known transcription factors that would group more than 2,000 proteins based on the role these molecules play in the cell. The possible result: an updated textbook (A. Brivanlou, J. Darnell, "Signal transduction and the control of gene expression," Science, 295:813-8, Feb. 1, 2002). The idea originally centered on creating a lecture tool to teach cell biology students about transcription factors—proteins that act as a gene's "on/off" switch. Darnell, Vincent Astor professor of molecular biology, says, "Grouping by structure is useful to a point, but the functional characteristics of the proteins in the cell aren't maintained strictly on a structural basis." Defects in transcription pathways often serve as a breeding ground for oncogenes. Darnell predicts that this new grouping may give a clearer view of what causes cancer. "We're throwing this out there and hoping that it's useful to people," he says. Darnell and Brivanlou have pitched their idea to Artie Burke, coauthor of the textbook Molecular Cell Biology. Darnell says he hopes that this classification form will be included in the book's latest edition. "I think this will be a useful framework to discuss transcription factors... that's why we took the pain to do this." —Hal Cohen

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