Genetic and immunological analysis of the structure and assembly of thick filaments in the striated body wall muscles of the nematode, Caenorhabditis elegans will be pursued. Many mutants with alterations of thick filament assembly and organization have been isolated in C. elegans. Monoclonal antibodies will be produced to the protein components of thick filaments isolated from the nematode body muscles. The localization of these components in muscle by immunofluorescence and in isolated filaments by electron microscopy from both wild-type and muscle-defective mutant nematodes will be studied. In vitro reconstitution experiments involving wild-type and mutant structures will be attempted. The understanding of the mechanisms of thick filament assembly and how specific gene products perform specific roles in such a process has significance as an example of a detailed scheme for morphogenesis relevant to many areas in cell and developmental biology, as a model for human inherited non-metabolic diseases, and for the physiology and development of human cardiac and skeletal muscles.
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