Title: Single molecule investigations of thick and thin filament regulation, in vitro and in vivo

In this seminar I will discuss how we have exploited single molecule imaging approaches to understand the regulation of myosin. Why is this important? Since skeletal muscle comprises ~35% of our total mass this places a huge metabolic load on our systems. Therefore, controlling the amount of energy consumed is of paramount importance to survival. Regulation comes in two flavours: from the thin filament, and from the thick filament. Using a series of in vitro single molecule approaches we have gained an understanding of the mechanism of regulation at the thin filament level, finding that there are three clear states of activation, and more recently that relaxation is an active process. This latter observation is relevant to hypertrophic cardiomyopathy, the most common genetic heart condition. In addition, we have been investigating thick filament regulation by understanding how myosins behave in myofibrils, furthermore we discover the effects of phosphorylation and drugs on alterations in activation; these may have important implications in the study of skeletal myopathies.

Aula Querzoli LENS