Biological and Biomedical Science
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Paula I. Watnick

Division of Infectious Diseases

Department of Pediatrics

Children's Hospital
Enders Building, Room 760
300 Longwood Ave.
Boston, MA 02115
Tel: 617-919-2918
Fax: 617-730-0254
Email: paula.watnick@childrens.harvard.edu
5 postdoctoral fellows, 1 technician

Vibrio cholerae is a marine organism, a symbiont of arthropods, and a pathogen of humans that causes severe and pandemic diarrheal disease.  V. cholerae survives in the aquatic environment through adhesion to the surfaces of particulates, plants, and insects.  When ingested, V. cholerae passes through the human gastrointestinal tract to colonize the distal small intestine and colon.  Cholera toxin, which is secreted into the intestinal lumen, is taken up by intestinal epithelial cells where it activates adenylate cyclase leading to opening of cAMP-responsive ion channels.  Our laboratory investigates the strategies V. cholerae uses to colonize aquatic surfaces, the arthropod intestine, and the mammalian intestine.

1) Environmental signals that induce biofilm formation.  Our laboratory has identified multiple environmental signals that activate Vibrio cholerae biofilm formation.  We are currently dissecting the signal transduction cascades that sense these signals.

2) The host-pathogen interaction using a Drosophila model.  Ingestion of pathogenic V. cholerae by Drosophila melanogaster induces an infection with many similarities to cholera. We use the powerful genetic tools available in the fly to identify components of the innate immune system that modulate susceptibility to disease.

3) Colonization of the mammalian intestine.  Colonization of the mammalian intestine is the first step in V. cholerae infection.  Our laboratory uses a mouse model to study the mechanisms by which V. cholerae colonization factors produce a successful infection.

 

 

References:

  • Moorthy S, Watnick PI, Identification of novel stage-specific genetic requirements by whole genome transcriptional profiling of Vibrio cholerae biofilm development, Mol Microbiol, 2005; 57: 1623-1635.
  • Blow N, Watnick PI, Vibrio cholerae infection of Drosophila melanogaster mimics the human disease cholera, PLoS Pathogens, 2005; 1:92-98.
  • Van Dellen K, Houot L. and Watnick PI, Genetic Analysis of Vibrio cholerae monolayer formation reveals a key role for ΔΨ in the transition to permanent attachment. J Bacteriol, 2008; 190: 8185-8196.
  • Berkey C, Blow N, Watnick PI, Genetic analysis of Drosophila melanogaster susceptibility to intestinal V. cholerae infection. Cell Microbiol. 2009; 11:461-474.