Paula Ivonne Watnick
Commensal intestinal bacteria participate in digestion of the host diet, provide essential amino acids and vitamins, and secrete metabolites that control many aspects of host intestinal function. In contrast, pathogens disrupt intestinal function. The goal of the research in our lab is to understand the basic principles underlying control of host intestinal innate immunity and metabolism by pathogenic and commensal bacteria. We use bacterial and host genetics in tandem as well as transcriptomics, metabolomics, and microscopy to trace the signaling pathways that control bacterial behavior and host response. The pathogens we have focused on are the diarrheal pathogen Vibrio cholerae and the pathobiont adherent-invasive Escherichia coli. We currently use the common fruit fly Drosophila melanogaster and human enteroids to model the host intestine. The following general areas are currently under study in the laboratory:
- Control of intestinal innate immunity by the microbiota in a Drosophila model. We have recently uncovered evidence that a specialized intestinal cell known as the enteroendocrine cell coordinates the host intestinal innate immune response to commensal microbes by sensing the short chain fatty acids produced by the microbiota. We are currently exploring the possibility that microbial metabolites control chromatin remodeling in enteroendocrine cells. Drosophila is an excellent model in which to study this phenomenon as there are drivers that specifically target each intestinal cell type.
- Vibrio cholerae high cell density quorum sensing regulation as a symbiosis factor. Several years ago, we developed a model in which we orally infect Drosophila melanogaster with V. cholerae. A V. cholerae biofilm forms in the Drosophila intestine, and this leads to wasting and death within days. We have discovered that high cell density quorum sensing attenuates V. cholerae virulence in this model. We are investigating the metabolic changes that occur in V. cholerae in response to high cell density signaling and the effect of these changes on the host intestine.
- Association of Vibrio cholerae proteins with the inner membrane as a regulatory mechanism. We have discovered a group of proteins involved in carbohydrate metabolism that are reversibly associated with the V. cholerae inner membrane. We are currently exploring regulation of this membrane association, its impact on the V. cholerae transcriptome, and the implications for V. cholerae virulence.
- Control of intestinal innate immunity by host and microbe-derived small molecules. Recently, other investigators have discovered how to differentiate stem cells from human biopsy specimens into small spheres known as enteroids containing all the cell types of the intestine. We are currently using enteroids to understand the intestinal innate immune response. We have treated these enteroids with short chain fatty acids, small molecules produced by the host, and vaccine strains carrying adjuvants to determine how these treatments impact the intestinal innate immune response and susceptibility to invasion by adherent-invasive Escherichia coli.
Enders Building, Room 760.2
300 Longwood Avenue
Boston, MA 02115