The role of the Rb family in skeletal muscle adaptation

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The role of the Rb family in skeletal muscle adaptationMetabolism is the chemical processes occurring within an organism that is necessary for the maintenance of life. Our research program is to understand the novel role of the retinoblastoma susceptibility (Rb) family (Rb, p107 and p130) of transcriptional repressor proteins in regulating metabolism. To date, very little is known for how and why they function in controlling the metabolism of cells. Our short-term goal outlined in this proposal is to examine their role in skeletal muscle metabolism. Skeletal muscle is a highly plastic tissue with the ability to undergo functional changes, including their metabolic state. These adaptive changes occur within the muscle fibers and their stem cells. We will address molecular, cellular and physiological roles of the Rb family in skeletal muscle metabolic adaptations by the following 3 objectives:1. To discover a metabolic role for how the Rb family influences muscle fiber formation. Muscle fiber type changes are a read-out for the metabolic state of the skeletal muscle. The function of the Rb family during stem cell differentiation into fiber types will be characterized. Using this strategy, we expect to find a metabolic role for the Rb family during muscle fiber formation. 2. To understand Rb family-mediated metabolic adaptation in muscle under physiologic stress. Specifically, we will determine how the Rb family members are involved in facilitating muscle metabolic changes associated with exercise and diet. This will allow us to find how stress influences stem cell function and skeletal muscle fiber changes in the context of the Rb family members.3. To determine the influence of the muscle microenvironment on the Rb family and muscle metabolic adaptation. We will determine the effect of nutrients and metabolic inhibitors on the Rb family members in muscle stem cells and fiber changes using isolated muscle fibers. This will provide knowledge about how nutritional and metabolic pathways affects the Rb family in the context of the muscle microenvironment. Our results will highlight a new role of influencing metabolism for the Rb family. This insight will benefit the scientific community by providing innovative information about how muscle metabolic changes occur.