PMI members organize courses and provide research training in muscle, cell motility, and the cytoskeleton through graduate programs in the School of Medicine, the School of Arts and Sciences, and the School of Engineering and Applied Science.
See below to learn more about our courses and research.
Mechanism and Regulation of Muscle Contraction
Three types of muscles, skeletal, cardiac and smooth, convert metabolic energy to mechanical force and work for myriad functions in the organism. The wide impact of understanding the molecular mechanism and control of muscle contraction in cell biology should be emphasized. The molecular mechanism of muscle contraction is similar to that of cellular and organelle motility which are prerequisites for normal cell development and function. Contractility is also a model for biological energy transduction and enzymology in general. The relationship between the amino-acid sequence, structural biology and functional output of motor proteins and contractile proteins are being studied intensively in many PMI labs.
As with non-muscle motility, the general paradigm cells use for generating motion is a motor protein sliding along a linear filamentous track. This architecture was first discovered in muscle cells because these elegant machines express and assemble concentrated and highly periodic interdigitating arrays of myosin and actin filaments that are particularly amenable to structural, mechanical and biochemical studies. The filaments do not change length when the muscle contracts, but they slide relative to each other using energy liberated by hydrolysis of ATP to ADP and phosphate. The relationships between the biochemical steps of ATP hydrolysis, the mechanical development of force and filament sliding and the molecular structural changes are the major goals of this research. State-of-the-art technologies, such as laser photolysis of 'caged' substrates and signalling molecules, time-resolved electron microscopy, optical traps (laser tweezers), fluorescence polarization spectroscopy and molecular genetics are applied to discover the mechanism of chemical-to-mechanical energy conversion.
Control of muscle contraction takes many forms, including calcium signaling, phosphorylation by specific kinases and receptor-effector signal cascades. As with contraction, signaling and control of muscle cells act as prardigms for corresponding proccesses throughout cell biology. Modern biophysical and molecular biological techniques are being applied to detail the molecular mechanisms of these pathways. PMI laboratories are prominent in developing new techniques with broad impact.
Daniel Safer, Ph.D.