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Researchers working in two cutting-edge but quite different realms of theoretical genetics, both with significant practical applications, are among those chosen in this year's MacArthur Fellows Program Awards, also known as the MacArthur "genius awards." James J. Collins, biomedical engineer at Boston University, and Loren H. Rieseberg, botanist at Indiana University at Bloomington, will each get $500,000 to spend any way he wishes.Rieseberg, who learned of his good fortune last Tuesday (September 30), told The Scientist that he is planning to use his money to hire an illustrator and research help for a book on plant speciation he'll write on sabbatical next year. He'll also spend money in his lab, finding ways to test function in the several candidate genes for plant speciation that he and his colleagues have identified, and applying the trendy techniques of RNA interference to their work. And then there's the popular book about sunflowers he wants to write, which will involve hiring someone to photograph all of the hundreds of sunflower species.Collins, who got his electrifying phone call last Monday (September 29), said he is still stunned. "It's all been so sudden. I do plan to think very carefully about how to use the award. That's a pretty boring answer, but it's the answer right now."Work by Rieseberg and his colleagues could help to clarify what may be the hottest political topic in science: genetic manipulation of crop plants. One recent paper showed that a Bacillus thuringiensis (Bt) transgene can spread from cultivated to wild sunflowers, increasing the latter's resistance to pests and its seed production. Another paper showed that a transgene that helps sunflowers resist fungus has the opposite effect; it is unlikely to spread rapidly to wild sunflowers because the transgene doesn't affect their seed production. "Everyone has focused so much on whether or not the crops and wild plants will hybridize, when what's really important is that a transgene is not going anywhere if it doesn't provide a fitness advantage," Rieseberg said. Theirs is a practical approach that could—and should—be applied to any transgene, he argued. "It's fairly straightforward to introduce a transgene just by backcrossing into wild populations and looking at the fitness effects of the transgene. That's what should be done over and over again with different transgenes, because each one will be different. So far it hasn't been done very much."The award cited Rieseberg's work on plant speciation, which has involved innovative experiments replicating the birth of new hybrid species and demonstrating that genomes of synthetic hybrids produced in a greenhouse are very similar in gene content to hybrid species that occur in nature. He also developed an influential new theory of chromosome speciation. He and his colleagues have shown that many species boundaries are porous, permitting gene flow, and just last summer demonstrated that hybridization can facilitate major ecological transitions and adaptive evolutions.The foundation emphasized the work Collins and his colleagues have done on balance and locomotion, which demonstrates that "noise" added to signal can enhance sensory and motor function. In a paper published last week in The Lancet, for example, they show that vibrating gel insoles help people balance, especially elderly people.But in a series of high-profile papers in the past couple of years, they have been doing something completely different: devising mathematical ways of revealing gene regulatory networks. Most recently, Collins and his colleagues constructed a model of regulatory interactions in a nine-gene subnetwork that is part of the system that governs antibiotic resistance in Escherichia coli. The researchers say that, even with no previous information about the network, the model can identify the regulatory role of individual genes in the network, along with network control points and genes that influence a drug's activity in a cell. It can also predict gene expression changes and network behaviors in response to perturbation by a given compound.This could be big news for the pharmaceutical industry, which needs reliable ways to find out not just whether a candidate drug hits a particular target of interest in a cell, but what else it hits. "Many compounds are dirty and hit a lot of other targets. This leads to complications, side effects, and toxicity. We showed that once you obtain the network, you can identify the direct hits of a compound within that network," Collins said.Perhaps not surprisingly, Collins is cofounder of the fledgling Cellicon Biotechnologies in Boston. "We're trying to harness these reverse engineering techniques to gain insight into the underlying networks and to help inform development of new drugs," he told The Scientist.The MacArthur awards, announced yesterday (October 5), are legendary for annually bestowing large sums on each of two dozen or so unsuspecting beneficiaries who are deemed creative and original. Not only may recipients use this windfall as they see fit, they are not required to write reports or do anything else to account for it. The selection process is secret, and recipients usually profess astonishment at being chosen. But in fact, they tend to be prominent in their fields. Both Riesenberg and Collins publish regularly in top journals, and this year Collins achieved a publishing trifecta, with papers in Science, Nature, and PNAS.The awards are notable for covering a huge range of creative fields. Other winners this year include historians, writers, social activists, and among the artists, a blacksmith. But more than half of the 24 award recipients for 2003 work in science, especially the life sciences and medicine.Among them are archaeologist Guillermo Algaze of the University of California, San Diego, an expert in the organization of the earliest cities; and computational geometer Erik Demaine, who studies folding and bending at the Massachusetts Institute of Technology. Peter Gleick, president of the Pacific Institute for Studies in Development, Environment, and Security, is a conservation analyst specializing in fresh water resources. Physicist Deborah Jin studies low-temperature quantum mechanics at the Joint Institute for Laboratory Astrophysics in Boulder, Colo. Gerontological nurse Sarah H. Kagan is a professor at the University of Pennsylvania; and Ned Kahn of Sebastopol, Calif., is a science exhibit artist.Physician Jim Yong Kim, of the World Health Organization in Geneva, develops ways of treating major diseases in poor countries; and physician Nawal Nour, of Brigham and Women's Hospital in Boston, specializes in female immigrants who have undergone ritual circumcision. Biochemist Amy Rosenzweig studies the structural basis for metabolism of transition metals related to disease at Northwestern University. Agronomist Pedro A. Sanchez, at the Earth Institute of Columbia University in Upper Grandview, NY, has pioneered solutions to problems of agricultural productivity in arid southern Africa; and biophysicist Xiaowei Zhuang, of Harvard University, tracks behavior of individual molecules to understand basic biochemical processes like enzymatic action or viral infection.

Two MacArthur 'geniuses' advance genetics

Half-million dollar prizes awarded for creativity in a wide range of disciplines

Oct 5, 2003

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