Understanding the fundamental links between mitochondria and muscle metabolism and disease

Striated muscles including skeletal and cardiac muscle makes up a major proportion of our body mass. Because of their high metabolic activity, striated muscle also requires a large amount of energy so it can perform important roles such as locomotion, pumping blood, keeping our lungs functioning and aiding in our vascular system working efficiently. Consequently, striated muscles consumes about 80% of the glucose from our blood following a meal, and plays an important role in maintaining a healthy energy balance. The primary way in which striated muscles generate energy, is through processing sugar and fat in the mitochondria. Given these important roles of muscle and mitochondria, it comes as no surprise that diseases or conditions that negatively impact on striated muscles, can have major consequences on our health and longevity. Indeed, genetic conditions that impact on mitochondria, muscle strength and activity can lead to muscular dystrophies and heart failure, whilst in born errors of metabolism can cause severe muscular dysfunction, metabolic disease and early death. However, the genes that cause these diseases are not well described, nor is the reason for why these diseases range from mild inconveniences to life threatening conditions of the young. Thus, studies aimed at understanding the genes and progression of these conditions are paramount in working towards treatments and cures. This project will use a range of molecular biology, genetic, pharmacological and bioinformatics techniques to study muscle conditions in pre-clinical models. The main aim of these studies is to understand the genes that cause these muscle defects, and to study their impact on chronic disease progression.