Skeletal muscle cell adaptations to exercise-related stressors

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Exercise introduces profound stress on skeletal muscle cells, which prompts them to adapt to make subsequent exercise less disruptive. These adaptations underlie improved physical fitness, which is important to optimal health and well being. Fundamental questions persist about how these adaptations to stress occur. First, exercise can be broken down into fundamental biochemical and biophysical stressors that affect the cells, such as increased metabolic demand and lowered oxygen levels. Furthermore, we know that cells have molecules that sense the stressors and activate other molecules via biochemical reactions. A set of molecules that transduces stressor information into the cell comprises a signalling pathway. Recent evidence indicates that signalling pathways are interconnected and thus form a network, which adds complexity to the way cells can respond to stressors. My research program seeks to understand the molecular regulatory network that operates inside skeletal muscle cells. The proposed research seeks to accomplish three objectives: 1) investigate how the stressors related to exercise influence skeletal muscle cell signalling pathways known to be essential for exercise adaptations, 2) investigate how the skeletal muscle cell signalling network integrates the stressors and coordinates the adaptations and 3) investigate the time it takes for adaptations to occur in response to exercise training and the rate at which these adaptations disappear once training ceases. My trainees and I will address these objectives by performing experiments that use a sophisticated cell culture model of exercise and by building computer models of the signalling network. The experimental and modelling work complement each other as the experiments provide data to validate the models and to verify their predictions, while the models inspire new questions that drive new experiments. Together, our experiments and computer models will provide unprecedented insight into longstanding questions regarding muscle physiology and the nature of cells in general. The unique quantitative focus of our research complements and strengthens existing world-class exercise and muscle physiology research in Canada. The knowledge generated from our research could eventually be applied to optimize how people exercise and to create better ways to grow muscle tissue for implantation into patients who have suffered muscle loss.