COBRE: Membrane Protein Production and Characterization

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EXCEED THE SPACE PROVIDED. The COBRE on Membrane Protein Production and Characterization (COMPPAC) is motivated by the disparity between the critical role of membrane proteins in biology and the well-recognized deficiencies in production and structural characterization of these molecules. We will address this challenge via a suite of five subprojects involving seven Pis from four academic disciplines at all faculty ranks, with all five of the lead Pis being either early-career or junior investigators. The scope of the research spans a spectrumfrom membrane protein overexpression, solubilization and purification, to structure-function studies based on crystallographic characterization, to predominantly functional studies of biomedically significant or related membrane proteins. The membrane proteins to be studied span a variety of structural and functional characteristics, including receptors, adhesion proteins and interfacial enzymes, and their relevance to several biomedically important conditions will be examined, including cancer, spermatogenesis and chemical warfare. The COBRE will have a strong interdisciplinary flavor by virtue of collaborations within and between subprojects, and as the initial subprojects acquire independent support, the scope of the research activities will be expanded by complementary research within several additional active membrane protein research labs. Core facilities support to be provided for protein production, structural biology and bioimaging is closely integrated with the substantial infrastructure for biomolecular research at the University of Delaware and the Delaware Biotechnology Institute. The COBRE will also foster the systematic application of the methods under development to membrane proteins in general, especially for the expression, purification and structural biology studies. This can have a significant impact on the membrane protein research community at large, and on the national infrastructure on membrane protein structural biology being developed within the NIH Roadmap.