Research Interest

Embo

Our research is focused on understanding the molecular basis of cell motility. Motor proteins are molecular machines that can convert the energy from ATP hydrolysis into force and motion. Myosin consists of a large superfamily of actin-based motor proteins that are involved in a wide variety of cell motility processes such as muscle contraction, organelle transport, and cell division. Although myosin motors have a well conserved structural core, they have very different biochemical properties. Thus, small changes in structure appear to have profound effects on the biochemical properties of myosin motors. The long-term goal of my research program is to understand the basic mechanism of energy transduction used by all myosin motors and to determine how different members of the myosin superfamily have fine tuned their biochemical and structural properties to perform specific cellular functions.

Biophysical properties of myosin. A combination of genetic engineering and fluorescence spectroscopic methods are used to examine dynamic structural changes in myosin. Examining specific conformational changes in myosin will reveal important details about how myosin binds to actin, and how myosin generates force and motion using the energy from ATP hydrolysis.

Regulation and enzymatic properties of non-muscle myosins. Another goal of my research is to express and purify various non-muscle myosins and examine their enzymatic properties using transient kinetic methods. Characterizing the enzymatic cycle of these non-muscle myosins will lead to a better understanding of their cellular functions. It is unclear how many non-muscle myosins are turned on and off in the cell. Another goal of my research is to characterize different mechanisms of regulation of non-muscle myosins, including ligand-induced structural changes, phosphorylation-induced structural changes, and interactions with other regulatory proteins that affect the biophysical properties of myosin.

Impact of disease-associated mutations in myosins. The impact of mutations in cardiac myosin associated with inherited cardiomyopathies and in class III myosins associated with deafness are being investigated. Fluorescence spectroscopic, kinetic, and cell biological approaches are used to to determine how the mutations disrupt myosin motor function with the goal of understanding how the mutations impact in vivo function and disease pathogenesis.