Origins of variation in muscle mitochondrial metabolism

我的项目探索了肌肉能量产生差异的起源和后果：肌肉新陈代谢是如何在需要时重塑的，以及组织和动物之间的新陈代谢机制是如何由于进化和发育而产生差异的。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控途径和那些负责特定组织和动物的独特特征的调控途径。 在下一个赠款周期中，我们利用不断增长的基因组信息数据库，开始梳理出物种间能量代谢差异的调控基础。我们对人类肌肉如何对生理条件做出反应有很好的理解，比如锻炼。然而，人们对物种之间的差异是如何产生的知之甚少。最近的问题集中在(I)哺乳动物谱系之间肌肉代谢特性的差异是如何产生的，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。这些研究有助于确定细胞和遗传途径，这些途径是自然界中看到的多样性的基础，让我们深入了解已知的对我们自己的新陈代谢至关重要的途径的进化起源。 拟议中的实验将为希望更好地了解细胞生物学、进化和生理学之间的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，这些培训可用于解决学术界和工业界的问题。

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.