Thesis work involved the identification and biochemical characterization of a novel actin binding activity in the large rod-shaped domain of dystrophin. I discovered that dystrophin interacts with F-actin via two distinct sites, separated by over 1200 amino acids and approximately 50 nm. This discovery led to a model for the interaction of dystrophin with actin filaments whereby dystrophin binds alongside the filament, thereby explaining the surprisingly low stoichiometry of the interaction. In addition, I found that the dystrophin homologue utrophin lacks both the cluster of basic repeats and its actin binding activity. These results have important implications for the design of gene-therapeutic protocols for the treatment of patients suffering from Duchenne Muscular Dystrophy.
Research projects aim to elucidate the molecular mechanisms of eukaryotic cell motility.
A single base pair substitution within the paired box of PAX3 in an individual with Waardenburg Syndrome Type 1. A new model for the interaction of dystrophin with F-actin. Journal of Cell Biology. A cluster of basic repeats in the dystrophin rod domain binds F-actin through an electrostatic interaction. Journal of Biological Chemistry .