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COMPUTATIONAL STRUCTURAL AND FUNCTIONAL GENOMICS

$270,000K22FY2001HGNIH

University Of California Berkeley, Berkeley CA

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Abstract

DESCRIPTION: (Applicant's abstract) I am a Sloan/DOE Postdoctoral Fellow in Computational Molecular Biology with a background in both Computer Science and Molecular Biology. This Genome Scholar Development and Faculty Transition Award will, during the development phase in Michael Levitt's group at Stanford, provide training and research experience in the application of computational methodologies to genome analysis. This will prepare me for the Faculty Transition phase, which directly supports my goal of establishing an innovative and productive independent group focused on computational molecular biology and genomics. The Award will provide resources allowing me to develop a research program in genome analysis as the human genome sequence is completed, structural genomics blossoms, and many other functional genomics data first become available. The principal research aim is to develop computational methods for structural and functional genomics, using the genome both as a base for investigation and as a resource to help answer biological questions. Structural genomics projects attempt to provide an experimental structure or a good theoretical model for every protein in all completed genomes. My work will involve organizing proteins into families according to homology, predicting structure from homology and constructing coordinate models, maintaining an information resource for structural genomics, developing methods for selection of proteins for experimental characterization, and analyzing solved structures to detect homologies and functional information. The computational functional genomics aspect of this project will primarily involve moving beyond pairwise sequence comparison in order to achieve reliable functional annotation of complete genomes. This includes the use of gene genealogies to trace gene histories and functional divergences, and "reverse genomics" comparison of multiple complete genomes to locate genes associated with characterized cellular or biochemical functions. I also plan to quantitatively combine sequence comparison with expression and other experimental functional data to improve computational molecular and cellular functional characterization.

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