Muscle is one of the most abundant tissues in the animal body and the primary producer of force for movement. A remarkable feature of muscle, at the cellular level, is the organized interdigitation of chemically distinct thin and thick protein filaments that translate the nanometer movements of molecular motors in the thick filament into animal locomotion. Thick filaments are known to be composed of the motor protein myosin, but the manner by which myosin molecules assemble into thick filaments of uniform length is still unknown and most likely involves additional regulatory proteins. This project studies potential roles for the regulatory protein flightin in the organization and function of muscle thick filaments in a model system, the flight muscle of the fruit fly Drosophila melanogaster. Insect flight muscle is known to be one of the most powerful muscles in the animal kingdom. A combination of biochemical and genetic experiments are used to define the functional properties of flightin, which generates oscillatory work, much like vertebrate cardiac muscle. The research also investigates the mechanism by which flightin contributes to the mechanical properties of flight muscle. This project combines classical genetics approaches with molecular biology, biochemistry, cell structure, and state-of-the-art molecular imaging and muscle physiology techniques. This multidisciplinary approach will result in a coherent, integrated view of the functional roles of flightin and provide valuable insight into the mechanism of thick filament assembly during muscle development, and the mechanism by which oscillatory muscles produce high power output.
This research has considerable broader impact both in both education and in the generation of biological reagents for the Drosophila and muscle research communities. Previous NSF funding to this lab has been instrumental in training undergraduate and graduate students, including the participation of students from underrepresented groups, and the current project continues this tradition.
