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We have carried out an integrative functional analysis on a variety of muscle proteins using the Drosophila model. Proteins include the myosin regulatory light chain, myosin, flightin, projectin, tropomyosin, and metabolic enzymes. For example, in a study of 3 phosphorylation site mutations in the regulatory light chain (RLC), we were able to trace deficiencies in oscillatory power from the molecular level to the organismal level. We demonstrated a graded reduction in mechanical and metabolic power production, wing beat frequency, and flight ability. X-ray diffraction studies in living flies confirmed that a reduced recruitment of power-generating cross-bridges underlay the drop in power output.

Mouse models of human diseases have become very important for the better understanding and treatment of humans. Familial hypertropohic cardiomyopathy, in particular, is a class of human heart disease caused by mutant genes for sarcomeric proteins and lends itself very well to study through transgenic mice. Mice possessing a specific genetic defect have been generated by our collaborators (Dr. Seidman and Dr. Robbins). We study the mechanical and kinetic consequences of the the genetic defects in thin strips of heart muscle. Because these specific genetic defects may or may not lead to precitable protein defects, these studies are shedding light onto the coupling of protein expression and its mechanical consequences.