Molecular structural basis of the effect of external load on the mechanical performance of skeletal muscle

This proposal will use time-resolved X-ray diffraction to determine the contribution of novel regulatory mechanisms in the myosin-containing thick filaments in fast-twitch skeletal muscles of mammals to the performance of those muscles in response to changes in external load. The protocols will mimic the normal functions of human skeletal muscles in everyday life, providing the fundamental mechanistic understanding to underpin the development of novel therapies for muscle weakness. The ID02 beamline with Eiger 2-4M detector is uniquely suitable worldwide to determine the relevant molecular structural changes in isolated muscle.