Skeletal muscle cell adaptations to exercise-related stressors

运动给骨骼肌细胞带来了巨大的压力，促使它们适应，以减少后续运动的破坏性。这些适应是改善身体健康的基础，而身体健康对最佳健康和幸福很重要。关于这些对压力的适应是如何发生的，基本问题仍然存在。首先，运动可以分解为影响细胞的基本生化和生物物理应激源，如代谢需求增加和氧气水平降低。此外，我们知道细胞中有感受应激源的分子，并通过生化反应激活其他分子。一组将应激源信息传递到细胞内的分子包括一条信号通路。最近的证据表明，信号通路是相互连接的，因此形成了一个网络，这增加了细胞对应激源的反应方式的复杂性。 我的研究项目试图了解在骨骼肌细胞内运行的分子调控网络。这项拟议的研究试图实现三个目标：1)调查与运动有关的应激源如何影响已知对运动适应至关重要的骨骼肌细胞信号通路；2)调查骨骼肌细胞信号网络如何整合应激源并协调适应；3)调查运动训练响应适应发生的时间以及训练停止后这些适应消失的速度。我和我的受训者将通过使用复杂的运动细胞培养模型进行实验，并通过建立信号网络的计算机模型来解决这些目标。实验和建模工作相辅相成，因为实验提供了数据来验证模型和验证它们的预测，而模型激发了新的问题，推动了新的实验。总之，我们的实验和计算机模型将为有关肌肉生理学和一般细胞性质的长期问题提供前所未有的洞察力。我们研究的独特量化重点补充和加强了加拿大现有的世界级运动和肌肉生理学研究。我们的研究产生的知识最终可能被应用于优化人们的锻炼方式，并创造出更好的方法来种植肌肉组织，以便植入遭受肌肉损失的患者体内。

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.