The long term goal of my research program is to understand the design of muscular systems. This involves performing experiments that facilitate the integration of information from molecular, cellular and whole animal studies. This approach is unusual and important because scientists generally work either on molecules, cells or whole animals but not on all three. This approach is crucial because there are large gaps in our knowledge of the principles by which animals use their muscles. An ultimate goal of this integrative approach is to understand enough about the molecular (e.g., crossbridges, Ca pumps) and macroscopic (e.g., joints, muscle arms) components of muscular systems, so that we can develop a comprehensive model that enables us to understand and predict how alterations in one parameter (e.g., crossbridge detachment rate) might affect motor performance. With the recent developments in biophysical, whole animal, and musculo-skeletal modeling techniques, we are for the first time in the position where we can relate molecular properties (e.g., crossbridge kinetics) to whole animal function in meaningful way. The frog, Rana pipiens, presents a superb model to proceed to this level. First, the jumping muscles are nearly pure in fiber type, and all the fibers are maximally recruited during jumping. Further, frog fibers are amenable to biophysical techniques, and jumping is amenable to biomechanical analysis. Our goal will be to 1) measure the sarcomere length changes and activation pattern of the major extensor muscles during jumping, 2) drive the isolated muscles through these in vivo length changes and stimulation pattern, and measure the resulting force and power output, 3) construct an anatomically and physically accurate model of the frog muscular system. This """"""""virtual animal"""""""" will enable us to transduce our understanding of isolated muscle to whole animal locomotion and to test specific hypotheses about the design of the frog muscular system. 4) We will make a series of biophysical measurements on frog muscle fibers from which we will construct a simple molecular-based model of muscle which can be integrated into the overall model of the frog. We will then manipulate molecular properties in the model and observe the effect on jumping performance. Ultimately, elucidation of the principles of how healthy motor systems work may be useful in 1) understanding disease/injuries of the motor/cardiovascular systems, 2) designing computer systems for aiding movement in the handicapped, 3) designing pharmacological and genetic interventions for muscle disease states, 4) understanding the functional basis of training/ rehabilitation, 5) choosing appropriate skeletal muscle for heart pumping assist.
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