Faculty of University of Illinois at Chicago (UIC), in collaboration with the major institutions in the Chicago area such as University of Chicago (UC) and the Argonne National Lab (Argonne) seek NIH funding to acquire a high-field wide-bore NMR system at a 1H frequency of 700 MHz or higher for development of new solid-state NMR (SSNMR) experiments on structural studies of biomolecules. The proposed purchase of an ultra-high- field SSNMR system responds to increasing demands and lack of ultra-high-field SSNMR instruments for biomolecular applications in the US. The proposed system also complements the UIC's existing ultra-high-field systems (800 MHz and 900 MHz) at the Center for Structural Biology in the medical center area because these narrow-bore systems equipped with cryoprobes are incapable of SSNMR experiments. The new spectrometer to be housed in an existing NMR room in the UIC Chemistry Department will be within a commuting distance (~30 min) from other Chicago-area institutions such as Argonne, UC, and Northwestern. Chicago's central location at a traffic hub of the Midwest also makes our site suitable for the unique ultra-high-field wide-bore NMR instrument dedicated for SSNMR in the Midwest. The new instrument will be will be a driving force of new interdisciplinary research and inter-institutional collaborations using SSNMR in this area. The new instrument will serve for our department members (150 graduate students, 20 postdoctral fellows, and 24 faculty) and other researchers (~50) in the Chicago-area institutes including UIC, UC, and, Argonne to perform advanced research in a number of areas including (a) structural biology of amyloid proteins and membrane proteins by SSNMR, (b) protein misfolding kinetics, (c) NMR and SSNMR characterization of novel natural products, organimetallics, and drugs, (d) drug metabolism, (e) membrane association of amyloid, (f) protein structures and dynamics of protein complexes, and (g) analysis of biomembrane bi-layer. In addition to the novel applications of NMR stated above, we will develop new SSNMR methods that would impact broad areas of medical and biological research. In particular, (1) we will develop novel methods to significantly enhance sensitivity in order to attain 10-fold time saving in SSNMR experiments for biomolecules and biomaterials. (2) We will offer new tools for structural analysis of amyloid proteins and membrane proteins, which have been major bottle necks in the current structural proteomics.
The impact of this proposal to the public health is two fold. First, our target includes amyloid proteins and membrane proteins, which are associated with various diseases;structural and functional studies proposed here will provide insights into the mechanisms of the diseases. Second, the state-of-the-art SSNMR instrument easily accessible to researchers in UIC and other Chicago-area institutions will generate excellent opportunities of research-based education on structural analysis of biomolecules by NMR and advanced NMR methods;undergraduate and graduate students will be uniquely trained as future work force in environments relevant to the public health.
