Analyzing the Role of Dysferlin in Skeletal Muscle in Vitro and in Vivo

Robert Bloch, PhD

University of Maryland School of Medicine (Baltimore, MD)

Dr. Bloch is a Professor in the Department of Physiology in the Graduate Program in Life Sciences, School of Medicine, University of Maryland, (Baltimore, MA).

Research Projects

Objective: 
Assess the role of dysferlin in skeletal muscles in vitro and in vivo

We have been studying dysferlin-null and control myofibers in culture, with and without drug treatments and with and without transfection with variants of dysferlin, to learn how dysferlin promotes protection of muscle from damage and repair after damage, and how drugs targeting the calcium channel proteins of the triad junction can help prevent damage to dysferlin-null muscle. Our previous work showed clearly that most of the dysferlin in adult skeletal muscle concentrates in the transverse tubules (TT), and that the TT and Ca signaling are more easily damaged when dysferlin is absent.  In the course of our studies, we identified a set of dysferlin mutants that do not target the TT, but that may show activity in different assays.  We have also found that the sensitivity to drugs that protect dysferlin-null muscle against damage changes following injury.  In our current studies, we continue to examine the pharmacology of dysferlin-null muscle, before and after injury.  We are also continuing to test two alternative hypotheses for the role of dysferlin:  1. Dysferlin must be present in the TT to be active in protecting muscle against damage, or 2. Different parts of the dysferlin molecule, and different locations within the cell where it can concentrate, can mediate different activities of the protein in mature myofibers.  Our experiments involve assays of Ca transients in control and dysferlin-null myofibers injured by hypo-osmotic shock and, in collaboration with Dr. Noah Weisleder (Ohio State University), by laser wounding