Craig D. Ellermeier, Ph.D.
Ph.D., University of Illinois at Urbana-Champaign, 2003 |
Assistant Professor of Microbiology Campus address: 3-630 BSB Mailing address: 51 Newton Rd. 3-630 Bowen Science Building Iowa City, IA 52242 Phone: 319-384-4565 Email: |
Bacterial cell signaling
Cells often respond to changes in their environment by altering gene expression. To accomplish this they are required to detect changes in their environment and then transduce that signal from outside the cell to a transcriptional response inside the cell. My research focuses on understanding the basic molecular mechanisms involved in how cells sense and respond to extracellular signals.
In response to nutrient deprivation the gram positive bacterium Bacillus subtilis forms a spore which remains dormant and capable of surviving a number of stresses. Sporulation is initiated by the activation of a response regulator, Spo0A. The activity of Spo0A is not uniform across all cells of the population, in fact two subpopulations of B. subtilis exist, Spo0A-ON cells and Spo0A-OFF cells. The Spo0A-ON cells produce a toxin, SdpC, which is secreted and kills the SpoOA-OFF siblings. Normally, the Spo0A-ON cells resist the toxic effects of SdpC by producing a membrane protein, SdpI, which provides immunity to the toxin. The immunity protein is only produced when extracellular toxin is present. Interestingly, SdpI is also required to induce its own expression in response to extracellular toxin sequestering a transcriptional repressor, SdpR, to the membrane. The sequestration of SdpR by the SdpC/SdpI complex inhibits the activity of the repressor thereby allowing increased transcription of sdpI, and immunity to the toxin. I’m interested in characterizing the SdpR/I interaction using genetics and biochemistry to gain insights into the molecular events which accompany the detection of extracellular signals.
I’ve found the SdpC toxin is recognized not only by SdpI but also by a second signal transduction protein PrsW which controls activation of the alternative sigma factor σW. Activation of σW occurs by proteolytic cleavage of an anti-sigma factor RsiW in a process termed regulated intramembrane proteolysis (RIP). The RIP pathway is a highly conserved regulatory system present in both Gram positive and negative bacteria as well as Eukaryotes. A RIP pathway utilizes two proteases; a site-1 protease which initiates the activation of the system and a highly conserved site-2 protease which cleaves its substrate within the membrane only after cleavage by the site-1 protease. The newly discovered PrsW protein appears to be a novel site-1 protease that responds to SdpC (and other toxins) by initiating cleavage of the anti-σW factor, RsiW and leading to activation of σW. I’m interested in determining how PrsW detects antimicrobial peptides and what events are required to trigger cleavage of the anti-sigma factor.
Recent publications
Ellermeier, C.D., and Losick, R. Novel protease governing regulated intramembrane proteolysis in Bacillus subtilis. Genes and Development 20:1911-1922, 2006.
Ellermeier, C.D., Hobbs, E.C., Gonzalez-Pastor, J.E., and Losick, R. A three-protein signaling pathway governing immunity to a bacterial cannibalism toxin. Cell 124:549-559, 2006.