Origins of variation in muscle energetics

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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.