Susan Lowey

Biography

Dr. Lowey received her Ph.D. in Physical Chemistry at Yale University. Her characterization of the myosin molecule continued as a postdoctoral fellow at Harvard University, and forms the basis of a long career on the structure and function of contractile proteins. Following a decade at the Childrens Cancer Research Foundation, Harvard Medical School, she brought her biochemical expertise to a team of biophysicists at the newly founded Rosenstiel Basic Medical Sciences Research Center, Brandeis University. Since 1998 she has been Professor in the Department of Molecular Physiology & Biophysics at the University of Vermont.

Research Interest

Dr. Lowey’s laboratory studies the role of myosin in muscle contraction. Many aspects of the interaction between myosin and actin have been elaborated since the sliding filament theory of contraction was originally proposed in the 1950’s, but a detailed mechanism of how ATP hydrolysis is coupled to force generation is still not available. Current structural models have focused on conformational changes occurring at the interface between the globular catalytic domain of myosin and the actin filament. Many of the point mutations implicated in inherited hypertrophic cardiomyopathy are found in the actin-binding regions of the myosin molecule. One experimental approach has been to engineer point mutations in the gene for cardiac myosin heavy chain and express the mutant myosin in mice or more recently in rabbits. The isolated and purified myosin can be analyzed by transient kinetics to understand the effect of the mutation on the basic actomyosin contractile cycle. To probe the structural consequences of a mutation, actin filaments can be decorated with mutant myosin, and the complex characterized by electron cryomicroscopy and image analysis (Volkmann et al., 2007, PLoS ONE 2(11):e1123. This biochemical/biophysical research will provide students with a basic understanding of biological motors and the contractile process in healthy and diseased states of heart muscle.