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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR029021-01
Application #
7840575
Study Section
Special Emphasis Panel (ZRG1-SBIB-L (30))
Program Officer
Birken, Steven
Project Start
2010-08-10
Project End
2011-08-09
Budget Start
2010-08-10
Budget End
2011-08-09
Support Year
1
Fiscal Year
2010
Total Cost
$1,014,958
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Li, Tao; Zhang, Zhen; Kolwicz Jr, Stephen C et al. (2017) Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury. Cell Metab 25:374-385
Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena et al. (2016) Normalization of NAD+ Redox Balance as a Therapy for Heart Failure. Circulation 134:883-94
Choi, Yong Seon; de Mattos, Ana Barbosa Marcondes; Shao, Dan et al. (2016) Preservation of myocardial fatty acid oxidation prevents diastolic dysfunction in mice subjected to angiotensin II infusion. J Mol Cell Cardiol 100:64-71
Chiao, Ying Ann; Kolwicz, Stephen C; Basisty, Nathan et al. (2016) Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts. Aging (Albany NY) 8:314-27
Kolwicz Jr, Stephen C; Liu, Li; Goldberg, Ira J et al. (2015) Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress. Diabetes 64:2817-27
Park, Joshua; Wicki, Jacqueline; Knoblaugh, Sue E et al. (2015) Multi-parametric MRI at 14T for muscular dystrophy mice treated with AAV vector-mediated gene therapy. PLoS One 10:e0124914
Berkseth, Kathryn E; Guyenet, Stephan J; Melhorn, Susan J et al. (2014) Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: a combined immunohistochemical and magnetic resonance imaging study. Endocrinology 155:2858-67