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GENOMICS Center for RNA Interference Probes Fly Genome Screening Facility Open to Harvard and Other Researchers Last May, Howard Hughes investigator Norbert Perrimon, HMS professor of genetics, opened what may be the world's first genomewide RNA interference (RNAi) screening facility for drosophila, now located in the new research building. Any researcher in the world may apply to use the facility, known as the Drosophila RNAi Screening Center. The high-throughput technology allows scientists to systematically block expression of different proteins in fruit fly cells. And the facility picks up most of the tab, asking only for reimbursement for reagents and 384-well plates to set up the cell assays. "Our goal is to make the technology available to many labs without the time, money, or access to the expertise," Perrimon said. "Importantly, we also will build a database of information, a sort of RNAi-ome." The public database eventually will allow functional comparisons across many studies and promote a standardized format for easier computational analysis. Three months ago, Perrimon's research group and international collaborators demonstrated the effectiveness of the technology in a preliminary screening of 1,000 genes. Led by postdoctoral fellow Amy Kiger, the study identified 160 genes involved in controlling cell shape, one third of which had not been functionally characterized in fruit flies. They reported their findings in the October 2003 Journal of Biology. RNA interference knocks down the function of a gene by interfering with the messenger RNA before it can make a protein from the unaffected DNA blueprint. The Perrimon lab and their German collaborators have now created a double-stranded RNA library to block the function of each of the 16,000 drosophila genes. Their follow-up paper using the full library of double-stranded RNA is due to be published in the Feb. 6 Science. Researchers can use the screen to rapidly and systematically identify genes that kill cells, protect against pathogen infection, suppress oncogenes, help cells fuse, or affect aspects of signal transduction, Perrimon said. So far, six different research groups have screened their assays at the center. Once a research project has been accepted by the center, it usually takes about three to six months to develop a good assay with appropriate controls, said Susan Armknecht, manager of the screening center. Once that is done, it takes less than two weeks to run the screen, followed by the analysis. The center employs two full-time bioinformatics support staff, who are developing ways to help visiting researchers get the most from their data. Perrimon modeled the RNAi center on the HMS Institute of Chemistry and Cell Biology, which performs large-scale screens of chemical libraries to identify compounds in cell-based assays. Eventually, researchers may be able to merge the two approaches for potentially interesting studies, he said. Most of the funding for the center comes from the National Institute of General Medical Sciences, with seed money from the Howard Hughes Medical Institute and HMS. More information is available at http://flyrnai.org. --Carol Cruzan Morton