NIH Chemical Genomics Center

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After beginning scientific operations in 2005, the NCGC reached full staffing and production during the reporting year. The Center is now working with over 100 researchers worldwide, and during the year performed over 50 high-throughput screens on molecular targets and cellular phenotypes important for virtually every area of biology and disease, including cancer, heart disease, infectious diseases, and neurological disorders. During this year, the NCGC fully operationalized its titration-based Quantitative High Throughput Screening (qHTS) paradigm, and demonstrated that it significantly improves the efficiency of screening over conventional methods. The NCGC Informatics Division built an entirely new infrastructure to process and extract automated conclusions from the vast amount of data qHTS produces (routinely producing 2-5 million data points in a single experiment), and is preparing those programs for publication and dissemination. Also during the year, the NCGCs Chemistry Division reached full staffing, allowing the rich screening and informatics data to be used in medicinal chemistry optimization campaigns to develop and publish a variety of new chemical probes. Among these were a group of new chaperone leads for Gaucher Disease, a human lysosomal storage disease (published in PNAS 104:13192-7), Alzheimer Diease (published in Neurobiology of Disease doi:10.1016/j.nbd.2007.07.018), and Schistosomiasis (publication in press). In all, production metrics included >18,000,000 compounds screened, >2,250,000 concentration-response profiles generated, >233 million data points generated, and >21,000,000 data fields deposited into PubChem. The NCGC expanded its already-extensive outreach program during the year, in order to both educate the academic community about chemical genomics methods and capabilities, and assist researchers in their assay development efforts. NCGC staff delivered over 60 invited lectures worldwide during the year, from New York and Los Angeles to Japan, Germany, and Spain. In order to extend its educational reach further, the NCGC Assay Development Manual was updated and reached version 4.1 on the NCGC website (www.ncgc.nih.gov), and the NCGC published a comprehensive review of assay development for HTS in Nature Chemical Biology (3:466-79).