DESCRIPTION (provided by applicant): The candidate is a junior investigator at Mayo Clinic who is interested in how changes to skeletal muscle proteins contribute to the pathophysiology of Type 2 Diabetes. In particular, skeletal muscle mitochondria are the primary site of fuel metabolism and the development of insulin resistance with obesity appears to be linked to a decreased ability for mitochondria to function properly. His career objective is to investigate the contribution of mitochondrial function to Type 2 diabetes progression with a focus on cellular mechanisms that maintain protein health. The immediate career goal is to have protected research time to establish the connection between changes to insulin sensitivity and mitochondrial protein damage. In order to meet these goals, the candidate has developed an effective mentoring team in diabetes research (Dr. Nair), proteomics analysis by mass spectrometry (Dr. Bergen) and bioinformatics (Dr. Kocher). The training application includes new skills in proteomics and bioinformatics to identify damaging post-translational modifications to proteins during high fat feeding and how protein degradation with exercise training may be beneficial to remove damaged proteins. The approach will establish a research theme of determining the contribution of mitochondrial dysfunction to Type 2 diabetes. The resources and career development at Mayo Clinic provide outstanding opportunity to successfully complete the proposed project. At the completion of the award, the candidate will be well suited to perform mechanistic animal studies along with translational research in humans. RELEVANCE: Mitochondria are the primary site for fuel metabolism in skeletal muscle and the deterioration of mitochondria is implicated in the development of Type 2 diabetes. The current application seeks to understand how damage to mitochondrial proteins is regulated during changes to insulin resistance. It is hoped the results will help future therapies to treat or prevent Type 2 diabetes.

PUBLIC HEALTH RELEVANCE: Type 2 Diabetes is a major public health issue with high economic and social costs. It is necessary to understand the cellular factors contributing to Type 2 Diabetes to develop new approaches to treat and prevent Type 2 Diabetes.