Throughout his career, Dr. Sellers has focused on understanding the structure, function, and regulation of myosins. First discovered in skeletal muscle, myosins now comprise a superfamily of more than 40 classes throughout the animal and plant kingdoms. These motor proteins interact with actin to initiate movement or shuttle cargo within the cell and play an important role in many physiological and pathophysiological states; mutations in individual myosin genes are responsible for diseases including hypertrophic cardiac myopathy, blindness and deafness disorders, and neurological defects.
Dr. Sellers’s early work focused on the regulation of the myosin II isoforms found in smooth muscle and non-muscle cells. As new myosin isoforms were discovered, his interests shifted to also include studies of these “unconventional” myosins. Dr. Sellers has focused on studying myosin diversity as a means of understanding meaningful molecular differences that give rise to disparate functions. His interdisciplinary laboratory brings together a breadth of experience in fields such as developmental biology, biochemistry, cell biology, biophysics, and engineering and encompasses studies of systems ranging from single molecules to Drosophila.
Dr. Sellers’s interdisciplinary approach enables him to push the boundaries of visualization and understanding at the single molecule level. He and his colleagues have made several seminal contributions to understanding myosin as a mechano-enzyme. To measure the force and movement generated by a single molecule, Dr. Sellers and his colleagues have devised and built systems for optical trapping and super-resolution techniques that quantify movement of single molecules along actin filaments in vitro at nanometer resolution. They showed conclusively that myosin Va is a very tightly coupled enzyme—for every step it takes along an actin filament, it hydrolyzes a single ATP—in a finding published in Nature in 2008.
Dr. Sellers is also at the forefront of studying the kinetics of myosin interactions and their regulation. He and his colleagues have demonstrated that conformational changes determine whether several myosins are active or inactive and that multiple binding partners can regulate that transition. Dr. Sellers’s team has been able to visualize myosin in both active and inactive states through electron microscopy at up to two-nanometer resolution.
While Dr. Sellers is using electron microscopy to complement mechanical and kinetic studies to further his molecular levels of understanding, he and his colleagues are also pursuing cell biological and organismal approaches to study changes in cellular localization of single myosin molecules as a tool to answer functional questions in the context of single cells.
Meet the Team
James Sellers, Ph.D.
James Sellers graduated from the University of North Carolina at Chapel Hill in 1974 with a B.S. in chemistry and from Brandeis University in 1980 with a Ph.D. in biology and joined the NIH in 1979, where he is currently a Senior Investigator heading the Laboratory of Molecular Physiology. In 2012, Dr. Sellers was named Dean of the NIH-Oxford-Cambridge Scholars Program. Dr. Sellers was NHLBI Mentor of the Year in 2005. In 2012, Ohio State University Medical Center honored him as the Emil Bozler Distinguished Lecturer. He has authored or coauthored more than 175 papers and currently serves on the editorial boards of Bioarchitecture, Biophysical Journal, Journal of Biological Chemistry, and Journal of Muscle Research and Cell Motility. He is a member of the Biophysical Society, American Society for Cell Biology, and American Society of Biochemistry and Molecular Biology.