The broad, long-term objectives of this research are to understand the molecular basis of stretch-activation in muscles. Stretch-activation is an intrinsic property of all muscle types, but the underlying mechanisms for regulation and control are poorly understood. This research program will use the fruit fly (Drosophila) as model system for relating molecular-level structure to tissue- and organism- level function.
The specific aim of this project is determine the role of calcium in regulating force generation and power output in the Indirect Flight Muscles (IFMs) of Drosophila. These measurements will provide essential information for testing among current models of the molecular basis of stretch-activation and its physiological regulation. The proposed research seeks an integrative understanding that links molecular biophysics to whole organismal performance. Because of the longstanding importance of IFM as a model for muscle ultrastructure, as well as the emerging importance of Drosophila as a genetic model system, these results will have broad implications for our understanding of muscle physiology. Since human cardiac muscle also relies on stretch- activated for proper muscular function, the results from this work will provide important information about how stretch-activation works and help develop research tools to screen for genes that contribute to muscular degeneration in humans. Relevance to public health: Cardiovascular disease is the leading cause of death in the United States, affecting well over half a million Americans annually. By providing a means of better linking molecular mechanisms to intact muscular function, the basic research findings and the technology developed in this proposal will be of great benefit to the future study, prevention, and treatment of muscular diseases. ? ? ?