Molecular motors lie at the heart of biological processes ranging from DNA replication to cell migration. The principal goal of our research is to understand the physical mechanisms of these nanoscale machines. We use single molecule tracking and manipulation to characterize conformational changes coupled to substeps in fuel consumption, and integrate our real-time measurements with complementary crystallographic and biochemical data to develop detailed models of structural dynamics and mechanochemistry. We further challenge our understanding by designing and testing structural variants with novel properties that expand the functional range of known biomolecular motors. In the process, we are developing an engineering capacity for molecular motors with tunable and dynamically controllable physical properties, providing a toolkit for precise perturbations of mechanical functions inside or outstide of living cells.
Our recent efforts have focused on 1) mechanochemical analysis of the supercoiling motor DNA gyrase; 2) developing new technologies for molecular motors research, including high-resolution torque spectroscopy and multimodal single-molecule microscopy methods; and 3) engineering novel cytoskeletal motors, including myosin and kinesin motors that respond to external signals such as light. In current research, we are using tools developed in the laboratory to push our understanding in two complementary directions: new single-molecule approaches can help us develop increasingly high-resolution descriptions of individual motor mechanisms, while engineered molecular motors may now be used as reagents to probe the determinants of collective motor functions, bridging scales from molecules to cells and tissues.