College of Science Distinguished Speaker: Regulation of Bacterial Behavior via Two Component Systems

College of Science Distinguished Speaker
Regulation of Bacterial Behavior via Two Component Systems

Dr. Ann Stock
Associate Director of the Center for Advanced Biotechnology and Medicine
Distinguished Professor, Department of Biochemistry and Molecular Biology
RBHS, Robert Wood Johnson Medical School
View website here.

Register Here for Zoom Link

Abstract:
Responsiveness to environmental cues is a fundamental characteristic of living organisms. Bacteria, as single-celled organisms, are commonly subjected to large changes in their environments and must elicit appropriate adaptive responses to changing conditions to survive and thrive. Such responses are especially important for interactions of bacteria with hosts, whether beneficial or pathogenic, and are thus important to both health and disease. "Two-component system” (TCS) phosphotransfer pathways involving a sensor histidine protein kinase and a phosphorylation-activated response regulator that generates the output response comprise a versatile regulatory scheme that occurs in hundreds of thousands of bacterial regulatory systems.
Signal transduction relies on concerted regulation of biochemical activities and signaling protein concentrations. Expression levels of TCS proteins have been shown to be under sophisticated control to match phosphorylation activities. However, the relationship between the concentration of a response regulator transcription factor and the number of its DNA binding sites remains largely unexplored, and it is generally assumed that transcription factors are in great excess to their binding sites. We investigated this premise using decoy binding sites expressed on plasmids to vary transcription factor to binding site ratios. In the model TCS investigated, we found that the concentration of the transcription factor is not in great excess to, but rather, approximately at capacity for the number of its DNA binding sites. The balance between the concentration of a transcription factor and the number of its binding sites may have a profound role in transcription regulation and suggests the potential of transcription factor inhibition as a therapeutic target. Structures of Staphylococcus aureus response regulator transcription factors AgrA and VraR have revealed novel binding sites that might be exploited for such purposes.

Speaker Bio:
Ann Stock is Distinguished Professor of Biochemistry and Molecular Biology at Rutgers-Robert Wood Johnson Medical School and Associate Director of the Center for Advanced Biotechnology and Medicine. She also serves as Co-Director of the Rutgers Graduate Training Program in Biotechnology. Stock obtained an A.B. in Biochemistry (1979) and Ph.D. in Comparative Biochemistry (1986) from the University of California at Berkeley working in the laboratory of Professor Daniel E. Koshland, Jr. and pursued postdoctoral studies in structural biology at Princeton University and Brandeis University with Professor Greg Petsko as a Damon Runyon-Walter Winchell Postdoctoral Fellow and a Lucille P. Markey Scholar. She joined the Center for Advanced Biotechnology and Medicine at Rutgers University in 1991. Her research interests focus on bacterial signal transduction and the molecular mechanisms that allow cells to elicit adaptive responses to changes in their environments. She participated in the discovery and characterization of a fundamental two-component phosphotransfer mechanism, now known to mediate the majority of bacterial signaling. Her current research focuses on understanding how specific features of signaling pathway architecture provide regulation of gene expression that is optimized for the specific needs of individual systems. Stock's research has been supported by NIH and NSF funding, NIH MERIT and MIRA awards and the Howard Hughes Medical Institute (1994-2011). She is an elected fellow of the American Association for the Advancement of Science (2006) and the American Academy of Microbiology (2007).  She served as editor for Journal of Bacteriology (2011-2021), and currently is a member of the advisory board and editorial board for PLoS Biology. Stock is president-elect of the American Society for Biochemistry and Molecular Biology (ASBMB).

Intended Audience:
Those with interest in the topic. All are welcome.