Funds are requested to establish a state-of-the-art, high-resolution NMR facility for the study of biological systems. The facility which is to occupy the first floor of the new wing of the Biochemistry Building, Department of Biochemistry, University of Wisconsin-Madison (under construction), is designed to handle the severe problems of resolution and sensitivity encountered with biological macromolecules and in vivo preparations. The facility is to be based on two commercial multinuclear spectrometers (a 9.4 T wide bore spectrometer and an 11.8-16.5 T) narrow bore spectrometer) and an off-line data station for analyzing data. The instrumentation has been chosen to optimize the collection and analysis of two-dimensional NMR data sets and for carrying out biomedical NMR experiments requiring the ultimate in spectrometer sensitivity. The center will endeavor to provide the latest equipment and techniques in high-resolution, multinuclear magnetic resonance experimentation for collaborative and service projects covering several biomedical areas: structure and function of proteins, nucleic acids, and natural products; active sites and mechanisms of enzymes; modes of action of drugs; and physiological levels of metabolites in living cells and organisms. In addition to the primary function of providing effective research tools to these users, the facility will engage in instrumental development and will explore novel biomedical applications of NMR spectroscopy. Core research projects include homonuclear and heteronuclear two-dimensional NMR spectroscopy of macromolecules, isotopic labeling of biomolecules for NMR analysis, and multinuclear magnetic resonance studies of viruses, living cells, and intact tissues. The progress and administration of the facility will be reviewed regularly by an Advisory Committee of experts in the field of biological NMR, who will also evaluate the research proposals of long-term users. An Instrumentation Consultant Board will provide advice on development of equipment and techniques. A local Steering Committee, consisting of facility staff and representatives from the major user departments on campus, will deal with short range concerns.
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