Origins of variation in muscle mitochondrial metabolism

肌肉线粒体代谢变异的起源

• 批准号: 170572-2012
• 负责人: Moyes, Christopher
• 金额: $ 4.74万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569587
• 关键词: Origins; variation; muscle; mitochondrial; metabolism

My program explores the origins and consequences of variation in muscle energy production: how muscle metabolism is remodelled when needed and how differences in metabolic machinery arise between tissues and animals as a consequence of evolution and development. By comparing and contrasting models and experimental approaches, we hope to distinguish between regulatory pathways that are broadly conserved among animals and those that are responsible for unique features of specific tissues and animals. In the next grant cycle we take advantage of the growing database of genomic information to begin to tease apart the regulatory basis of interspecies differences in energy metabolism. We have a very good understanding of how a human muscle can change in response to physiological conditions, such as exercise. However, very little is known about how differences arise between species. The proximate questions focus on (i) how differences in muscle metabolic properties arise between lineages of mammals and (ii) whether the regulators that are critical in mammals are shared with primitive vertebrates. These studies help define the cellular and genetic pathways that are the underpinnings of diversity seen in nature, giving insight into the evolutionary origins of pathways known to be vital to our own metabolism. The experiments proposed will provide many training opportunities for students hoping to gain a greater understanding of the interactions between cell biology, evolution and physiology. Students will also gain important technical training that can be used to tackle questions in academia and industry.

我的计划探讨了肌肉能量产生变化的起源和后果：肌肉代谢在需要时如何重塑，以及组织和动物之间的代谢机制如何因进化和发展而产生差异。通过比较和对比模型和实验方法，我们希望区分在动物中广泛保守的调节途径和那些负责特定组织和动物独特特征的调节途径。 在下一个资助周期中，我们将利用不断增长的基因组信息数据库，开始梳理物种间能量代谢差异的调控基础。我们对人体肌肉如何响应生理条件（如运动）而变化有很好的了解。然而，人们对物种之间的差异是如何产生的知之甚少。最接近的问题集中在（i）肌肉代谢特性的差异如何在哺乳动物的谱系之间产生，以及（ii）在哺乳动物中至关重要的调节因子是否与原始脊椎动物共享。这些研究有助于定义细胞和遗传途径，这些途径是自然界中多样性的基础，使我们能够深入了解已知对我们自身代谢至关重要的途径的进化起源。 这些实验将为希望更好地了解细胞生物学、进化和生理学之间相互作用的学生提供许多培训机会。学生还将获得重要的技术培训，可用于解决学术界和工业界的问题。