Living cells include a plethora of molecular motors that perform a variety of vital tasks such as muscle contraction, cellular transport, or protein assembly. While the details of their operating cycles may vary, the operation of these motors is based on many common principles. In this talk, I will present our research into a specific molecular motor, myosin VI. Myosin VI is a processive motor that transports intracellular cargo. The directed transport of myosin VI takes place as a result of a coordinated complex ATP driven cycle that is not dissimilar from the mechano-chemical cycles of other molecular motors. Myosin VI is an interesting motor to study as it has been measured to have unusually large step size variations; it has also been reported to make both long forward and short inchworm-like forward steps, as well as step backwards. We have been developing minimal computational models to understand its operation and explore its complex processivity with respect to different mechanical and chemical properties of the motor as well as different environmental conditions. Our work helps us understand myosin VI as well as build a framework towards understanding molecular motors in general.

Nonmuscle myosins-2 are molecular motor proteins that interact with the actin cytoskeleton to power a manifold of processes that produce force and movement in cells and organisms. The research in my laboratory aims to define the molecular basis and the regulation of nonmuscle myosins-2 in physiological and pathological processes by probing their structure-function relationships. By applying sophisticated biochemical, biophysical, structural and cell biological methods and techniques, we quantitatively describe the functional capacities and limitations of nonmuscle myosin-2 motors in vitro. This knowledge can be applied in a reductionist approach in single molecule assays to build a physiological process from its components parts in vitro to (i) characterize nonmuscle myosin-2 motor function in cells and organisms, (ii) reveal regulatory mechanisms of myosin motor function, and (iii) develop tools to manipulate myosin motor function. By combining the power of in vitro and in vivo studies, our work contributes to the understanding of the physiological functions nonmuscle myosin-2 motors play in health and disease and in the development of tools to study them.