Research

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 catalytic domain and the light chain-binding domain in myosin. Many of the point mutations implicated in cardiac myopathies are found in these regions of the molecule. One experimental approach is to engineer point mutations in the catalytic domain or in the regulatory and essential light chains of either skeletal or cardiac myosin, and study their effect on the kinetic and mechanical properties of the actomyosin system. Another approach is to decorate actin filaments with myosin, and analyze the complex by electron cryomicroscopy and image analysis (Volkmann et al., 2007, PLoS ONE 2(11):e1123. This research should provide students with a basic understanding of biological motors and the contractile process.