Thomas Lab Theme
Molecular dynamics of energy transduction in muscle health and disease, using site-directed spectroscopic probes.
Our goal is to understand the fundamental molecular motions and interactions that are responsible for cellular movement, to determine the molecular bases of muscle disorders, and to apply these insights to therapeutic design. We approach this multidisciplinary problem with a wide range of techniques -- physiology, enzyme kinetics, molecular genetics, peptide synthesis, computer simulation -- but our forte is site-directed spectroscopy.
After attaching site-directed probes (spin labels, fluorescent dyes, phosphorescent dyes, or isotopes) to selected muscle proteins in solution or in living cells, we perform magnetic resonance or optical spectroscopy to directly detect the motions of the force-generating proteins, actin and myosin, or the Ca-regulating membrane proteins SERCA and phospholamban.
Our research involves several types of muscle, but the laboratory focuses increasingly on the heart. Indeed, our newest and most exciting direction is to use the principles of structural biophysics to design new molecular therapies for heart failure. This is an extremely ambitious and high-risk goal, but we are in a unique position to achieve it, due to an unparalleled combination of technologies, insights, and expert collaborators.