Overall This application is in response to PAR-16-415, Centers of Biomedical Research Excellence (COBRE) (P20). The proposed phase 1 center (P1C) is built on a strong foundation and long-term commitment to hibernation research at the University of Alaska’s Institute of Arctic Biology (IAB). The objective of the P1C is to use the expertise at IAB, in particular that of Dr. Kelly Drew, the PI, to build and strengthen the University of Alaska’s hibernation research infrastructure. The plan involves guiding the career development of three investigators, experienced in research, but who have yet to receive R01s from NIH, and to guide the career development of new investigators currently showing an interest in hibernation research. The long-term goal, likely beyond the life of the P1C, is to apply what is learned about the mechanisms underlying the physiological changes in hibernation to as yet unresolved issues relevant to metabolism and metabolic diseases such as disuse muscle atrophy, sarcopenia, obesity, type 2 diabetes and cardiovascular diseases in humans. The center will support the research and career development of both experienced scientists and those getting their start in research. The center will have a focus on all stages of research from basic through translational. By defining translational paths for discoveries in hibernation, the P1C will contribute to the career development of the investigators. Strong administrative and scientific leadership will accomplish the goals of this P1C through the following four Specific Aims (SA): SA1. Establish an organizational structure and research infrastructure that will support and promote a multidisciplinary framework to define mechanisms of metabolic adaptations in hibernating mammals. SA 2. Enhance the careers of P1C project PIs as well as new investigators leading pilot projects through the P1C in order to allow them to compete successfully for NIH individual research grants. SA3. Support research projects and pilot projects aimed at developing an understanding of physiological, genetic and gut microbial mechanisms in hibernation and how these mechanisms may play a role in treating disuse muscle atrophy or sarcopenia. SA 4. Support clinical research projects related to the theme of the center. Seasonal hibernators arguably display the most dramatic natural alterations in metabolism, appetite, diet, body composition and body temperature of any mammal across their annual cycle. Such extremes offer insight into regulatory mechanisms, and druggable targets that would be less obvious in traditional pre-clinical models. This P1C focuses on genetic and gut microbial mechanisms related to protein synthesis and preservation of skeletal muscle during prolonged disuse and fasting in hibernating mammals. Once completed new investigators will be equipped to identify and translate treatments to promote anabolic sensitivity and preservation of muscle mass and strength. Such discoveries have the potential to save $1 billion per year in health-care costs in the US by reducing risk for disability, hospitalization, and death in older and mobility impaired adults. The University of Alaska will establish a thematic, multidisciplinary research center in metabolism designed to translate fundamental knowledge gained from the study of mammalian hibernation to treat metabolic disease and improve metabolic health. The proposed Center of Transformative Research in Metabolism (C-TRiM) will be the first biomedical research center in the US to adopt a model of natural adaptations in metabolism as an approach to solve complex clinical problems in the treatment of metabolic disease.