Introduction to Research Seminar

Relaxation

Research in the Thomas lab focuses on protein structure and dynamics in skeletal and cardiac muscle, to determine the molecular mechanisms of muscle function and malfunction. Principal tools: optical and magnetic resonance spectroscopy, enzyme kinetics, and computational molecular modeling. A rotation project or thesis project, tailored to the student’s interests, can involve any of four muscle proteins (myosin, actin, calcium pump, phospholamban) and five spectroscopic techniques (fluorescence, phosphorescence, luminescence, EPR, NMR), and can focus on fundamental mechanisms, spectrosocopic techniques or theory.
Example 1 (see figure at left above): Express single-Cys mutants of myosin in cell culture, label them with fluorescent dyes, measure function at the single molecule level, use laser spectroscopy to measure myosin structural dynamics during ATP hydrolysis, use data to construct a new computer model of muscle contraction.
Recent Reference: Nesmelov, Y. E., R. V. Agafonov, A. Burr, R. T. Weber, and D. D. Thomas. 2008. Structure and dynamics of the force generating domain of myosin probed by multifrequency electron paramagnetic resonance. Biophys J, 95: 247-256.
Link to web site: http://ddt.biochem.umn.edu/Papers/S1WX.pdf
Example 2 (see figure at right above): Express functional mutants of phospholamban, related to heart disease, and use spectroscopy to determine effects of these mutations on protein structural dynamics.
Recent Reference: Winters, D. L., J. M. Autry, B. Svensson, and D. D. Thomas. 2008. Interdomain FRET in SERCA Probed by Cyan Fluorescent Protein Fused to the Actuator Domain. Biochemistry, 47: 4246–4256.
Link to web site: http://ddt.biochem.umn.edu/Papers/CFPFITC.pdf