This request is for funds to acquire a 4-channel 700 MHz nuclear magnetic resonance (NMR) spectrometer for solution studies of macromolecular structures and assemblies. The instrument will be equipped with a high-sensitivity triple resonance (1H, 13C, 15N) TCI cryoprobe that will substantially enhance sensitivity and permit analysis of samples with limited solubility. There is currently no high field instrument dedicated for macromolecular NMR at Oregon State University. The macromolecular NMR group previously utilized a Bruker DRX 600 MHz instrument that was purchased in 1994 but has been non-functional and mothballed since February 2012. The new instrument is critical for the needs of several NIH-supported Oregon State University researchers and other biomedical researchers from Oregon Health Science University, University of Oregon, Portland State University and smaller institutions in the region. Proposed major studies include the role of natively disordered proteins in macromolecular assembly, particularly in the dynein motor protein complex, protein deamidation in cataractous lens and aging, the role of protein dynamics in enzyme catalysis and mechanistic studies on various diseases including HIV and ALS. Continued productivity and growth to meet the needs of the existing NMR group and the expanding user base depend on this acquisition. The new instrument will be housed in the recently renovated space in the campus-wide NMR facility that is presently equipped with instrumentation dedicated to natural products and small organic molecules. Its incorporation into a pre-existing NMR center will ensure optimal maintenance and usage of this cutting-edge instrument. Oregon State University is committed to building a strong campus-wide NMR core that unites small molecule and biomolecular NMR facilities, and is supporting this proposal with a substantial match towards the cost of the instrument and recurring support towards operating costs to help build the user base and ensure the instrument is widely accessible even to students with limited access to funding. Dr. Barbar's protein NMR expertise and track record in acquiring multi-user instruments and interest in promoting a widely accessible facility enabling significant, biomedically relevant research make her uniquely suited to lead this effort. This purchase will be the first of its kind on campus and will have an immediate impact on the infrastructure at Oregon State University and participating institutions as it will enable cutting-edge science, foster highly collaborative biomedical research, and support the vibrant research environment in the State of Oregon.
Currently there is not a single high field instrument that is dedicated to protein work at Oregon State University or in the whole state of Oregon. The proposed high-field NMR instrument will support research aimed at understanding proteins and macromolecular assemblies involved in cellular trafficking, cataractous ageing of the eye, and enzyme mechanisms and catalysis. Knowledge of high-resolution structures and dynamics of these macromolecular systems will guide the design of novel therapeutics.
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