Chemical genetics of Src family kinases in embryonic stem cells

Description of projects available to graduate students:
A few years ago we discovered that selective pharmacological inhibitors of Src family kinases could either induce terminal differentiation or promote self-renewal of ES cells, suggesting the Src-family kinases control key signal pathways related to these biological outcomes. Because ES cells express multiple Src family members, we have taken a chemical genetics approach to the problem. This entails engineering functionally silent mutations into the kinase genes that renders them selectively sensitive to specific inhibitors. This allows specific pharmacological assessment of the role of single kinase activities on developmental outcomes. Our longer term goal is to identify kinases that can be specifically manipulated with selective inhibitors to either force renewal or guide desired developmental fates.

Techniques graduate student will learn:
ES cell culture; gene transfer; lentiviral transduction; in vitro differentiation