Grant: Fellowship - Priority Announcement: Dystonia (SHOPP)

The cause of many diseases often relates to hereditary factors passed on over generations and how those factors respond to environmental influences. When comparing the many genetic and environmental factors that contribute to the onset of neuromuscular or degenerative diseases, one commonality resurfaces continuously; failure of cells to send and receive signals vital to function and survival. In deed, multiple diseases of the nervous and muscle systems have at their core a break down in subcellular communication. While this break down is paramount to disease pathology, restoring cellular communication may lead to the development of novel therapeutic approaches. This proposal focuses on one group of proteins that function as a link between micro-structures of the cell called "organelles" and the scaffold that holds them in place. This protein family, known as "plakins," anchors the organelles responsible for housing DNA, synthesizing proteins and storing proteins until needed. The impairment of plakin protein linkages causes stress on these systems resulting in a complete breakdown in cellular function. This proposal will evaluate the contribution of these linker proteins to neuromuscular disease and determine whether restoring communication between the various organelles can alleviate disease symptoms. This proposal aims to identify novel gene products responsible for linking and maintaining organelle communication in neuromuscular and degenerative diseases. The work proposed herein will add to our understanding of disease by exploring the effect of cellular communication on cell function, evaluate novel therapeutics through functional recovery assessment and identify new protein and gene targets for therapeutic intervention.