Grant: Project Grant

Muscle contraction is a basic function of life, responsible for body movements, hear beating, breathing, to cite a few. Contraction is regulated by a variety of processes, including biochemical pathways that may change the way muscles work. Such changes may improve or inhibit contractions, and may eventually lead to weakness and muscular diseases, such a muscle dystrophies. The goal of this proposal is to investigate one regulatory mechanism called arginylation, a process by which muscle proteins receive arginine (Arg) from tRNA. We have pilot data showing that arginylation is a strong regulator of muscle contraction, and that lack of arginylation leads to muscle weakness and dystrophy. We will use novel and accurate methods that include sub-cellular structures and single molecules isolated from muscles to test the mechanism by which arginylation regulates muscle contraction. We will also test the effects of potential treatments for muscle dystrophy caused by lack of arginylation. This research will provide information that is needed for the understanding of the basic mechanisms of muscle contraction in health and disease, and may have implications for everyday life.