William W. Mattox, Ph.D.

Research

Our lab studies the alternative splicing of pre-mRNAs. In Drosophila, alternative splicing plays a central role in sex determination. We have been using the sex-determination system to study factors that influence alternative splicing and to determine the mechanisms by which they do so. Several of the proteins we are studying belong to the serine/arginine-rich (SR) family of splicing factors. These proteins usually bind to sequences located within exons, known as exonic splicing enhancers (ESEs) and activate nearby splice sites. We have found that an SR factors can repress splicing when bound within an intron. Using in vitro splicing assays and Drosophila genetics we are determining how splicing activation and repression differ. A second interest of the lab is in genetic models for muscular dystrophy. Recently we have developed a transgenic Drosophila model for facioscapulohumeral muscular dystrophy (FSHD) a poorly understood late-onset disease that affects specific muscle groups in humans. We are using genetic approaches to identify genes that reverse the muscle defects in these flies as a way to understand the molecular basis of the disease.