We request funds to purchase a new 800 MHz NMR spectrometer equipped with multiple receivers, a 1H/13C/15N cryoprobe with XYZ pulsed field gradient capability and an autosampler. This instrument will be installed in the Biomolecular NMR Facility (BNF) at the Medical College of Wisconsin. The BNF has supported the biomedical research programs of a diverse group of NIH-funded investigators in Milwaukee and southeast Wisconsin since its creation in 2000. Consistent with its record of major investments in NMR instrumentation and facilities, MCW has committed substantial matching funds to complete the purchase of the requested instrument. We describe projects from 6 major users with NIH funding and 5 minor users (2 with NIH funding) that will benefit from NMR instrumentation operating a magnetic field higher than the existing 500 and 600 MHz instruments housed at MCW. The user projects span a range of structure and functional dynamics studies on soluble and integral membrane proteins and their complexes with other proteins, nucleic acids, lipids, carbohydrates and other ligands. These projects will benefit from the requested instrumentation primarily due to the increases in resolution and sensitivity that accompany an increase in magnetic field strength. In addition, drug discovery projects and other types of automated screening will be enabled by inclusion of an autosampler, and large complexes including integral membrane proteins and glycoproteins that employ selective isotope labeling will benefit from direct carbon-13 detection. When installed, this instrument will be the only state-of-the-art 800 MHz NMR instrument in the State of Wisconsin. The Biomolecular NMR Facility is already equipped with the necessary infrastructure for successful installation and operation of an 800 MHz NMR and cryoprobe system (conditioned power, closed-loop chilled-water cooling system, and optimized environmental control). The new instrument will be maintained by a staff with experience in the operation and maintenance of high-field NMR magnets, cryoprobes and autosamplers. Users will be trained in the operation of the 800 MHz NMR and instrument time will be allocated using the existing NMR scheduling system. A standing local advisory committee provides oversight of the Biomolecular NMR Facility and its operations. Acquisition of the 800 MHz NMR instrument requested in this application will have a significant impact on NIH- funded biomedical research programs at MCW and other institutions in the region.
As a nationally prominent freestanding medical school, the Medical College of Wisconsin is committed to building a regional resource for structural biology to support key research programs in inflammation and infectious diseases, cancer, kidney diseases, diabetes, digestive diseases, and cardiovascular disease. The Biomolecular NMR Facility is the foundation of this effort. Enhanced access to cutting edge NMR technology requested in this application will contribute directly to the medical education and research missions of the College and its partner institutions in southeast Wisconsin. !