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Researcher | Research Overview

Our laboratory explores the interaction of commensal and pathogenic microbes with the host intestine using invertebrate and vertebrate model systems. We focus on regulation of bacterial metabolism and its impact on the host intestinal innate immune response and metabolic homeostasis. The following specific projects are ongoing in the laboratory:

  1. Conditional membrane association as a novel mechanism of bacterial transcription factor regulation.  We have identified two transcription factors that are regulated through reversible association with the bacterial inner membrane.  Transcription factor release from the membrane results from metabolically regulated post-transcriptional modification.  We are exploring the mechanism of membrane association, the impact of transcription factor membrane association on the bacterial transcriptome, and additional proteins that undergo reversible membrane association.
  2. Microbe-derived acetate control of histone acetylation in intestinal cells.  Using Drosophila as a model, we have identified a histone acetyltransferase expressed in intestinal cells that responds to acetate produced by intestinal bacteria.  This histone acetyltransferase co-regulates the intestinal innate immune response and lipid and glucose metabolism.  We are currently studying other intestinal functions regulated by this protein, the G-protein-coupled and innate immune receptors involved in the intestinal response to acetate, and biological sex-specific intestinal responses.  In addition, we are extending our observations to mammals using human enteroid-derived monolayers.
  3. Vibrio cholerae high cell density quorum sensing modulates the host intestinal innate immune response.  In both Drosophila and human enteroid models, we have discovered that bacterial quorum sensing modulates the intestinal innate immune response.  We are currently identifying the metabolites and bacterial structures responsible for this host response.

Researcher | Research Background

Paula Watnick received her undergraduate degree in Chemistry from Princeton University.  She subsequently was awarded an ITT international fellowship to study multi-dimensional nuclear magnetic resonance techniques in the laboratory of Prof. Kurt Wuthrich at the Federal Institute of Technology in Zurich.  She returned to complete a PhD in Biophysical Chemistry with Dr. Sunney Chan at the California Institute of Technology and an MD at Yale Medical School.  She trained in Internal Medicine at Beth Israel Hospital, Boston and in Infectious Disease at the Massachusetts General Hospital. Her postdoctoral research was conducted in the laboratories of Dr. Stephen Calderwood at Massachusetts General Hospital and Dr. Roberto Kolter at Harvard Medical School.  Dr. Watnick is a fellow of the Infectious Diseases Society of America, the American Academy of Microbiology, and the American Association for the Advancement of Science.


Researcher | Publications