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Putting eggs in a new basket

Medicine@Yale, 2010 - December

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Science for its own sake can also hatch payoffs, says a Yale geneticist

The laboratory of Lynn Cooley, Ph.D., is abuzz, not only with thousands of vials of live fruit flies, but with the excitement scientists experience when their research may cross a new threshold.

Cooley, an authority on oogenesis (egg development) in the fruit fly Drosophila melanogaster, says that until recently she would have characterized her work as “one hundred percent basic science.” But Cooley believes that recent findings in her lab have great potential for important new insights into human diseases such as muscular dystrophy.

Fruit flies are an all-too-common nuisance in kitchens around the world. But the ubiquity of these tiny flies belies their tremendous importance to biology. More than a century of work on Drosophila — a species that is unusually amenable to genetic manipulation and that reproduces and matures rapidly — has helped to unravel the molecular basis of core biological functions; over 60 percent ofDrosophila genes have counterparts in the human genome.

As a graduate student at the University of Texas–Austin, Cooley, now professor of genetics, cell biology, and of molecular, cellular, and developmental biology, studied proteins in the cytoskeleton, the “scaffolding” of cells. After earning her master’s degree, she left graduate school for a time and worked in the Yale lab of Dieter G. Söll, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry and professor of chemistry, “probably the most important influence in my career,” she says.

Though Cooley eventually received her doctorate from Texas, she conducted her dissertation research in Söll’s lab, studying the formation of histidine transfer RNA, a molecule involved in protein synthesis, in both yeast andDrosophila. During a postdoctoral fellowship with Allan C. Spradling, Ph.D., at the Carnegie Institution for Science in Baltimore, Md., Cooley began her explorations of oogenesis, working exclusively with Drosophila, and settled on the research niche and the model species that have defined her work ever since.

Cooley and those in her lab study not only the formation of eggs but the chambers in which eggs form, the flow of information and nutrients from so-called nurse cells to oocytes (developing eggs), changes in the cytoskeleton during egg development, and the role of muscle tissue in the progression of developing egg chambers through the Drosophila ovary.

In a 2008 study reported in Developmental Biology, Cooley and colleagues used a technique known as protein trapping to selectively tag specific components of ovarian muscle in Drosophila with fluorescent molecules, revealing surprising details of these structures that had previously received little attention from scientists.

“Then a student started trying to use the ovarian muscles as a model for studying mutations in proteins that cause muscular dystrophies,” says Cooley. “So now I feel at least I have a toe in the door for developing what we love about Drosophila oogenesis as a more translationally oriented model.”

But Cooley, who also directs the cross-campus Ph.D. program known as the Combined Program for Biological and Biomedical Sciences, emphasizes that the potential of Drosophila ovarian muscle as a model for human disease was revealed by basic research, which is in danger of being “downgraded” by society’s increased demand for translational work. It’s essential, Cooley believes, “for curiosity-driven science to continue, since you never know where efforts to figure out how biology works will lead.”

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