Dr. Nancy L. Martin
B.Sc., M.Sc., Ph.D, Associate Professor; Department of Microbiology and Immunology, Room 740 Botterell Hall Queen's University Kingston, Ontario, Canada K7L 3N6
Tel: 613 533-2460
Fax: 613 533-6796
nlm@queensu.ca



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Research Interests
1. Understanding how Salmonella typhimurium senses and adapts to changes in the environment
2. Understanding how these changes enhance bacterial survival
3. Using proteomics to understand how posttranslational events are used by bacteria to respond to changes in the environment.

DETAILS
We initiated an effort to characterize the disulphide oxidoreductases of Salmonella enterica serovar Typhimurium and found two periplasmic "foldases" that act to assist protein folding and are especially important to cell function when bacteria are growing in stressful conditions. One is a homologue of DsbA from E.coli, an enzyme that has been crystallized and has undergone extensive biochemical analysis. The second enzyme, called SrgA, is a substrate specific disulphide oxidoreductase that functions to oxidize cysteine resides in the PEF pilin subunit. As this work progressed we became interested in the transcriptional regulation of these foldases and this led to our current work studying the regulation of stress response proteins in S. typhimurium via a two component histidine kinase signal transduction pathway.

Bacteria survive in a multitude of diverse niches within the host organism and the ability to adapt to the specific challenges presented by each of these niches is key to establishing infection. Bacteria utilize several histidine kinase signal transduction pathways to sense and respond to changes outside of the cell. The lab currently focuses on two central issues related to sensing and responding to environmental stresses mediated by the Cpx histidine kinase pathway in S. typhimurium. First, we are attempting to map the types of environmental signals that stimulate specific stress response pathways. Using a proteomic-based approach coupled with transcriptional analysis of specific Cpx-responders we are comparing the responses of wild type and various mutant strains to a variety of stressors. Second, we are using a combined proteomic and biochemical approach to identify downstream responses in the Cpx signal transduction pathway. For example, we believe that a serine/threonine kinase is responsible for propagating the Cpx-initiated signal along one branch of the Cpx pathway. Serine/threonine kinases are poorly understood in bacterial systems, however our work is leading to an appreciation of how posttranslational events such as phosphorylation play a central role in bacterial adaptation and survival in the host. These studies will greatly enhance our understanding of ¬†bacterial virulence mechanisms and show us, perhaps, new approaches to controlling organisms that cause infectious disease.
Publications (PubMed)