This grant proposal requests partial funding support for a 600 MHz wide bore NMR spectrometer. The instrument will be located at the Center for NMR Research as part of an overall strategy to consolidate biomedically dedicated NMR instruments and promote collaborative research. The requested spectrometer will accommodate the growing needs of a major user group for in vivo microimaging and spectroscopy that cannot be met with the existing instrumentation. A major user group comprising eight separate research projects is identified, and members of the group have, or expect to have at the time of the grant award, peer-received NIH support. Justification and utilization of the proposed spectrometer are discussed in the introductory section of the research plan of the proposal, as well as within the individual research project description. The major strength of the proposal comes from the individual research projects themselves, all with clinical and biomedical relevance. Alzheimer's disease will be investigate mechanistically using both transgenic mouse models (Caserta) and structural peptide analysis (Krafft) which are complementary. Drug delivery and pharmacokinetics within the central nervous system are addressed in two projects (Groothuis and Wyrwicz). The Lurie Comprehensive Cancer Center collaborators have projects which investigate the carcinogenesis of breast cancer (Thor), causes of treatment failures in colon cancer (Knop) and two projects from major contributors to the field of tumor angiogenesis (Bouck and Soff). This broad representation within the Northwestern University Family focused on the areas of neuroscience and cancer is unmatched by any other scientific consortium in the Chicago metropolitan area. An additional strength of the proposal is the expertise of the multiple specialties available through the Center for NMR Research, and supported with resources necessary for successful implementation of experimental strategies.
