Striated muscle functions universally to generate biological force. We will study assembly and function if striated muscle. Our approach is largely genetic and uses the nematode Caenorhabditis elegans as a model organism. Genetic techniques are complementary to biochemical techniques for the study of muscle. Mutations that cause muscle dysfunction define genes required to construct a normal muscle cell. The nature of mutant defects provides insights into functions of the wild-type proteins. We will use genetics to investigate the structure and assembly o( nematode muscle. Mutants that are affected in the protein components of muscle will be identified and analyzed using a combination of genetic, molecular, and ultrastructural techniques. We will investigate the in vivo functions of myosin light chain proteins by identifying mutants that result from myosin light chain defects. Genes that are functionally related to myosin light chains will also be studied. We will investigate the assembly of thick myofilaments by characterizing mutations of a myosin heavy chain gene that interfere with assembly. We will identify specific amino acid residues of the myosin heavy chain molecule that are important for thick filament assembly. Thick filament proteins with which myosin interacts during assembly will be identified. Our long range goals are to determine how many genes are required for muscle assembly and function, to describe the protein products of those genes, and to understand how those proteins function during muscle assembly and contraction. This work is significant for understanding the genetic origins of human muscular disease.