The fundamental purpose underlying this request for the purchase of a 600 MHz wide bore 14T imaging spectrometer is to provide an innovative research group with a unique and powerful new tool that will provide a key for advancing its research programs beyond current limitations. This new instrument will make new experiments possible and enhance the productivity of a number of R01 projects studying cellular physiology in heart, muscle, cancer and the biology of aging, with emphases on mitochondrial function in intact cells. The University of Washington has established a Mitochondria and Metabolism Center at a newly built facility of the School of Medicine in Seattle, located at the South Lake Union campus with newly recruited faculty. This group is forming a unique resource, co-directed by Drs. Kushmerick and Tian and established by the cooperation of, and jointly administered by, the Departments of Anesthesiology and Pain Medicine and of Radiology in the School of Medicine and the Provost's Office. The proposed high field NMR spectrometer and micro-imager will be a primary technological focus of the Center and a unique instrument in the School of Medicine and at the University of Washington. The field of """"""""mitochondrial medicine"""""""" is expanding in importance. Both normal function and dysfunction of mitochondria play a central role in apoptosis and response to oxidative damage in addition to their role as the main source of metabolic energy in the cell. Innovative methodological and physiological advances developed by the users'grant projects have revealed insights into these mechanisms and clues for clinical applications. For example, with the addition of this high field spectrometer, we will be able to obtain critical functional data on mitochondrial function by magnetic resonance methods in conjunction with a wide range of biophysical, biochemical, physiological and molecular biological methods resident in the labs of our users. The facility will be maintained and quality control provided by MR expertise in the Department of Radiology and managed by both departments. The group of committed users includes well-funded projects in cardiac metabolism (Dr. Rong Tian), muscle metabolism and energetics (Drs. David Marcinek and Martin Kushmerick), aged muscle studies (Drs. Marcinek and Rabinovitch) and mouse tumor biology and molecular imaging (Dr. Donghoon Lee). In addition we have well-funded collaborators who are developing NMR techniques for their grants in myocardial stem cell and regeneration (Dr. Charles Murry), in mouse models of aging (Dr. Peter Rabinovitch), in cultured smooth muscle cells (Dr. Cecilia Giachelli) and in metabolomics (Dr. David Eaton). The proposed 14T instrument will be shared with those investigators and others within the University.
The research programs of the major and minor users of the magnetic resonance spectrometer proposed in this high-end instrument grant application encompass a wide scope of projects focused on furthering our understanding of and advancing diagnostic approaches for a range of disorders and diseases, including heart failure, aging, chronic and systemic diseases affecting muscle, and cancer. The equipment proposed is a very high resolution NMR spectrometer and microimager that will be used for testing hypotheses in basic science and serve to validate methods that can be translated into clinical applications and diagnostic procedures. The purchase of this equipment will allow these programs to advance in new and exciting directions, due to the advanced capabilities of this spectrometer.
