Muscle metabolism

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Work in my laboratory is focused on understanding how selected substances such as glucose and fatty acids are a) taken up into skeletal muscle, b) how they are stored and c) how they are used to generate energy for normal muscle contraction. In healthy muscles mobilization of glucose and fatty acids during different types of exercise depends on how hard one works. Alternatively, when, in the course of normal daily activities, fatty acid and glucose usage in muscle get out of balance, it can set the body on a path towards developing obesity or type 2 diabetes. However, exercise is recognized to be a good means to prevent such problems. The thrust of the proposed work is to determine how glucose and fatty acid use, in muscle, is controlled, by specific genes and by recently discovered signalling proteins, as well as developing an understanding of how muscles cope with, and adapt to exercise. A novel way to examine this in muscle is to alter experimentally the level of a protein, or a set of proteins, and then examine how this affects the entry and use of glucose and fatty acids in the muscle, or how this affects the ability of a muscle to adapt to exercise or exercise training. We have developed a state of the art method whereby we can alter the level of a protein within 7-14 days in a single muscle in a laboratory animal. This ability to now do so in live animals, rather than in cells in a lab dish, is a very important step forward. A key aspect in our work is that we alter proteins to levels that reflect the changes that can be expected to occur in muscle physiologically, i.e. in real life, as opposed to huge, abnormal changes that are often produced in genetically altered laboratory mice. Through our work we expect to develop a better understanding of the molecular processes that are involved in maintaining healthy metabolic processes in muscle.