Rock: Prokaryotic lipid metabolism

Our research program centers on prokaryotic lipid metabolism. A central theme is to define how the fatty acid biosynthetic pathway and membrane phospholipid formation are coordinately regulated with other major metabolic activities of the cell such as stable RNA synthesis and DNA replication. The techniques of genetics, molecular biology, biochemistry, chemical and structural biology are being applied to understanding the detailed interactions between the individual constituents of the coupled fatty acid/phospholipid biosynthetic pathway. Current research focuses on defining the regulatory signals and protein-protein interactions that control the overall rate of fatty acid biosynthesis, the detailed catalytic mechanisms of the individual enzymes, and the determination of the high-resolution structure of key regulatory proteins and transcription factors. We have purified all of the enzymes in the fatty acid biosynthetic pathway and the reconstitution of the fatty acid biosynthetic machinery in vitro provides a model to understand the interactions that occur between components of a complex biochemical network. These experiments are also relevant to the development of new targets for anti-bacterials and our group is affiliated with chemical and structural biologists at St. Jude to apply the basic information on the properties of the pathway enzymes to design effective inhibitors.