The project described here is a step towards my long term career goal which is to contribute fundamental knowledge regarding the molecular mechanisms underlying changes in gene expression in muscle as a result of injury or trauma and how this process is affected by aging. We have focused our studies on defining the regulatory mechanisms that control gene expression in satellite cells, the adult myoblasts that proliferate and differentiate in response to muscle injury, thereby regenerating damaged fibers. We are currently mapping the cis-regulatory elements controlling the muscle-specific enolase gene that, unlike most muscle- specific genes, is expressed at high levels in satellite cells. We propose here to isolate trans-acting factors that bind to the cis-regulatory DNA sequences by screening a bacterial expression library. We also propose to establish yeast as an experimental system and utilize genetic selection in yeast to isolate beta-enolases regulators, and proteins that interact with them to modify their activity. This award will guarantee the time required for me to gain experience and proficiency in yeast genetics.
