? In subproject C, """"""""Molecular Genetics of Ion Channels,"""""""" we are examining the nicotinic acetylcholine receptor, L-type calcium channels, and kainate receptors as well as the scaffolding proteins that couple to them. To obtain a detailed understanding of the molecular mechanism of the physiological consequences of the transgenic knock-in experiments, a series of biochemical and biophysical assays are carried out to characterize the modified protein. The targeted proteins are structurally characterized, and mutations aimed to abate the biological function without altering the protein structure are designed and then tested. The results provide a unique insight into the interpretation of the in viva findings from our knock-in experiments. Currently, the NMR instrumentation utilized for the structural studies is at a point of saturation and the research projects covered by this COBRE award (RR 15578) as well as other NIH-sponsored research efforts at Brown University cannot be aggressively pursued. Here we request funds for the acquisition of a cryogenic probe for the 600 MHz high resolution NMR which serves as the sole high-field instrument at Brown. Resulting in a 16-fold reduction in the time to collect data, the cryogenic probe is a cost-effective manner to address the critical demand for NMR measurement time that is currently limiting the scientific problems that can be undertaken. ? ?
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