Joan Taylor, associate professor of pathology at the University of North Carolina in Chapel Hill, was awarded an MDA research grant totaling $396,000 over a period of three years to study how muscle cells repair damaged membranes.
When a muscle contracts, it puts a great stress on the membrane that surrounds and encloses the muscle cell. That stress is reduced, and the membrane protected from rupture, by proteins that link the inside of the cell to the outside. Those proteins include dystrophin and the dystroglycan complex. Mutations in these proteins are the cause of Duchenne muscular dystrophy (DMD) and other forms of muscular dystrophy, which are characterized by repeated tears in the muscle cell membrane.
Membranes can repair themselves, says Taylor, “however, the specific mechanisms by which this occurs are incompletely understood.” Her team has identified a protein called GRAF1 that appears to be intimately involved in the repair process, and she has developed a mouse model to explore the function of GRAF1. She will now fully test the hypothesis that GRAF1 is necessary to promote membrane re-sealing, using a laser-based membrane injury model in skeletal muscle cells to identify the underlying mechanisms.
Taylor also will explore the capacity of GRAF1 (administered by a gene-therapy-based approach) to diminish muscle pathology in dystrophic mice. “These studies will undoubtedly lead to new and important directions for therapies to target a multitude of congenital dystrophies,” she says.
Funding for this MDA grant began Feb. 1, 2013.