Professor, Department of Microbiology and Immunology
Area of Interest
The ability to respond to stimuli is often considered a key characteristic of life. Living cells monitor properties of interest in their environment, transduce that information into a useable form, and execute appropriate responses to changing conditions. Errors in signal transduction can have serious consequences, such as cell growth in the absence of growth stimuli (i.e. cancer). Both prokaryotes and eukaryotes often encode information as phosphoryl groups transiently attached to proteins. Understanding the mechanisms and regulation of phosphoryl group transfer among proteins is thus of fundamental interest, as well as of practical significance to human health.
The Bourret Lab investigates the molecular mechanisms of transient protein phosphorylation in two-component regulatory systems, which are found in bacteria, archaea, eukaryotic microorganisms, and plants.
Although our research does not directly involve cancer, there are fundamental similarities across signaling pathways. For example, Ras proteins can catalyze their own activation and inactivation by binding GTP or hydrolyzing it to GDP, but Guanine Nucleotide Exchange Factors (GEFs) or GTPase Activating Proteins (GAPs) stimulate the intrinsic activity. Similarly, response regulator proteins in two-component systems can catalyze their own phosphorylation and dephosphorylation, but separate kinases and phosphatases stimulate the intrinsic activity. Furthermore, we discovered that phosphatases in two-component systems insert an amide residue into the active site to orient the attacking water molecule. This is reminiscent of the Ras GTPase mechanism.