Skeletal muscle cell adaptations to exercise-related stressors

运动会给骨骼肌细胞带来巨大的压力，促使它们适应，使随后的运动减少破坏性。这些适应是改善身体健康的基础，这对最佳健康和福祉很重要。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物化学和生物物理压力，例如增加代谢需求和降低氧气水平。此外，我们知道细胞具有感知压力源并通过生化反应激活其他分子的分子。将应激源信息转导到细胞中的一组分子包括信号传导途径。最近的证据表明，信号通路是相互连接的，从而形成一个网络，这增加了细胞对压力源的反应方式的复杂性。 我的研究项目旨在了解骨骼肌细胞内的分子调控网络。拟议的研究旨在实现三个目标：1）研究与运动相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）研究骨骼肌细胞信号网络如何整合应激源并协调适应; 3）调查运动训练产生适应性所需的时间，以及训练停止后这些适应性消失的速度。我和我的学员将通过使用复杂的细胞培养运动模型和建立信号网络的计算机模型进行实验来实现这些目标。实验和建模工作相辅相成，因为实验提供数据来验证模型并验证其预测，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见解。我们研究的独特定量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。从我们的研究中产生的知识最终可以应用于优化人们的运动方式，并创造更好的方法来生长肌肉组织，以植入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.