Origins of variation in muscle energetics

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。在下一个资助周期中，我们将探索肌肉中的基因如何被调节以控制生物能量酶的水平。结论1.PGC1是一种基因调节器，在许多情况下似乎对决定肌肉的线粒体含量很重要。我们将研究PGC1和相关基因是如何在脊椎动物进化史的早期出现的。我们还将研究原始脊椎动物PGC1的结构特点如何影响其功能。第二，每块肌肉都有为不同类型的活动量身定做的特性。例如，能量代谢酶的水平既可以支持长期运动，也可以支持短期、爆发式运动。由于每块肌肉都有相同的基因组成，目前还不清楚这些差异是如何在肌肉之间产生的。我们将通过比较不同肌肉细胞核中的基因调控水平来研究肌肉是如何变得特化的。结论三、具有耐低氧能力的动物有许多生理生化特长。例如，肌肉在不需要氧气的情况下可以产生能量的酶的水平不同。我们将研究调节这些酶的基因的因素，这些基因存在于三种不同的对氧依赖的相关鱼类中。因此，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。

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. In the next grant cycle we explore how the genes in muscle are regulated to control the levels of bioenergetic enzymes.     1. PGC1 is a gene regulator that appears to be important in determining the mitochondrial content of muscle in many contexts. We will examine how PGC1 and related genes arose early in the evolutionary history of vertebrates. We will also study how structural peculiarities in PGC1 of primitive vertebrates affect its function.     2. Each muscle possesses properties that are tailored to different types of activity. For example, the enzymes of energy metabolism occur at levels that can support either longterm exercise or short duration, burst exercise. Since each muscle has the same complement of genes, it is not clear how these differences arise between muscles. We will study how muscles become specialized by comparing the levels of gene regulators in nuclei of different muscles.     3. Animals with an ability to tolerate low levels of oxygen have many physiological and biochemical specializations. Muscles, for example, differ in the levels of enzymes that can produce energy without the need for oxygen. We will examine the factors that regulate the genes for these enzymes in three related fish that differ in oxygen dependency.    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.