This proposal request continued support for the Center of Magnetic Resonance (CMR) at the Francis Bitter National Magnet Laboratory. MIT (Grant RR-00995-18). During the coming five year grant period we plan significant upgrades of existing equipment, acquisition of new instrumentation, and research initiatives in several new areas. (1) The seven spectrometers currently operating in the facility will be upgraded with new transmitter, receivers, pulse programmer, computer, etc. (2) The facility will expand with the addition of nine additional instruments. These include a new addition to the facility, the Spatial NMR Laboratory containing five spectrometers, a new 600 MHz solution spectrometer, eventually two 750 MHz instruments and high field solid state NMR and EPR/DNP spectrometers. (3) New and continuing areas of interest in the core research program include: (a) RF gradient enhanced spectroscopy, (b) isotopic labeling and spectroscopy of RNA's and RNA/protein complexes, (c) imaging of solids, (d) structural studies of solids via dipolar recouping techniques (e) structural studies of large proteins including enzyme/substrate/inhibitor complexes, Beta-amyloid, bacteriorhodopsin, and halorhodopsin (f) CW and pulsed dynamic nuclear polarization, and (g) high frequency CW and pulsed EPR and ENDOR studies of paramagnetic enzymes and enzyme/inhibitor complexes. (4) The collaborative research effort will grow significantly and will include: Solution NMR investigations of (a) drug induced DNA degradation (Stubbe), (b) human sarcomas (Singer), (c) intermediates in protein folding (Kemp), (d) NMA binding domain (Lippard) (e) glycoprotein folding (Lansbury), (f) cell function and mRNA translation (Gehrke), (g) field dependence of 13C and 15N relaxation times in proteins (Wagner). Imaging studies will include (a) perfusion imaging (Rosen), (b) creatine kinase and brain energetics (Holtzman), (c) metabolism in human cancer xenograph (Jain), (d) diffusion of small solutes in cartilage (Burstein and Gray) and (e) spectroscopy and imaging of rabbit eyes (Chen). (5) The service component of the facility remains an important function as is evident by the 10 proposals from outside investigators who have or plan to use the facility frequently. (6) Plans for training and dissemination include course work in magnetic resonance, seminars and publication in scholarly journals.
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