Kathleen McDonough


  • Kathleen McDonough

    BIOMEDICAL SCIENCES

    The overall focus of Dr. McDonough's research program is bacterial pathogenesis. Two human pathogens, Mycobacterium tuberculosis (Mtb) and Yersinia pestis (plague), are addressed, and the importance of post-transcriptional regulation by small regulatory RNAs (sRNAs) in both organisms is a growing interest. sRNAs have been proposed as drivers of evolution, and one project involves the role of sRNAs in the emergence of epidemic strains of plague. Recent work in Dr. McDonough's laboratory has shown that the sRNA chaperone Hfq is required for Y. pestis growth at 37°C in vitro, but is entirely dispensable for the in vitro growth of Y. pseudotuberculosis. Hfq is identical in Y. pestis and Y. pseudotuberculosis, so it is expected that an interacting sRNA is responsible for these Hfq-associated biological differences. Dr. McDonough, in collaboration with Dr. Wade, used deep-sequencing to identify Yersinia-specific sRNAs, and found several sRNAs that showed species-specific differences in their Hfq dependence. Current studies are focused on exploring the biological basis of this species-specific dependence of sRNAs on Hfq, by using a combination of molecular genetic, biochemical, proteomic and microscopical approaches. These studies will elucidate the role of sRNAs in the biology of an important pathogen, while exploring its general role in evolution. This work has the potential to identify new plague-selective drug targets, and/or biomarkers that allow rapid differentiation of Y. pestis from Y. pseudotuberculosis in environmental and/or clinical samples.