of the application) The use of microarray technologies for transcriptional profiling has revolutionized the approach for characterizing the pattern of gene expression in cells under physiological and pathological conditions. The goal of this NIDDK Biotechnology Center is to build a comprehensive integrated microarray facility that will allow N1DDK researchers to create and analyze customized and commercial expression arrays as tools to gain new insights into disease pathogenesis and mechanisms, as well as permitting the characterization of the functional and regulatory pathways of disease related genes. Results from these studies will ultimately be applied for diagnosis, drug screening and treatment selection for diverse human disease states. We capitalize on the existence of a unique group of NIDDK funded investigators in the Harvard community and on the research, teaching and clinical strengths of the Beth Israel Deaconess Medical Center (BIDMC), Joslin Diabetes Center (JDC), Children's Hospital, Dana Farber Cancer Institute(DFCI) and other Harvard Institutions to create a multi-institutional NIDDK Biotechnology Center. This grant application focuses particularly on the strength of the combined diabetes, obesity, and nephrology programs at our institutions which are reflected in the selection of the 10 ongoing and 3 feasibility projects. A critical component of the Center, in addition to the Technology Core, is the inclusion of a highly interactive Bioinformatics Core. One of the strengths of the Center will be the unique capacity to provide web-accessible annotation, cataloging facilities and state-of-the-art bioinformatics analyses to all NIDDK investigators. This will enable researchers from all Projects to maximally utilize the expression data sets to determine functional dependencies among the known genes and Expressed Sequence Tags (ESTs) and direct further biological validation of these putative dependencies. The NIDDK Biotechnology Center will be organized into several Cores: the Technology Core, the Bioinformatics Core, and the Education Core which will be supervised and coordinated by the Administrative Core. The NIDDK Biotechnology Center will combine the complementary technologies of Affymetrix oligonucleotide microarray technology, custom made microarrays, and real time PCR with bioinformatics, and focus this expertise on problems in diabetes, obesity, and kidney disease. Knowledge gained from these investigations should provide insights into regulatory pathways and mechanisms of disease pathogenesis involved in diabetes, obesity and kidney disease. Finally, the Center will provide novel educational programs to attract other NIDDK researchers to microarray technologies and to disseminate knowledge gained by the investigations.