BBSRC Studentship: The intracellular lifestyle of Campylobacter jejuni: Roles of flagellar motility and pathogen-host crosstalk in the intestinal mucosa

Lead Research Organisation: Quadram Institute Bioscience
Department Name: Contracts

Abstract

Campylobacter jejuni is the most common bacterial cause of foodborne diarrhoeal illness worldwide. Upon entry in the intestine, Campylobacter uses its flagellar motility to penetrate the mucus layer overlaying the intestinal epithelium, adheres to the epithelial cells, and subsequently invades them. This process is thought to initiate the subsequent immune response to the infection as well as disease development. Alhough flagellar biosynthesis has been studied extensively, we still have limited understanding of its regulation in Campylobacter, and we also lack a firm understanding of the factors involved in adhesion and invasion of Campylobacter, and which cells in the intestinal mucosa Campylobacter interacts with. In this project we will 1) study the regulatory mechanisms involved in flagellar gene regulation 2) investigate the adherence and invasion mechanisms of Campylobacter, and 3) study the interaction of Campylobacter with dendritic intestinal cells (DCs) which are key initiators of the local immune response. Objective 1 will include study of mutants lacking regulatory proteins, regulatory RNAs and building blocks of the flagellum, followed by phenotypic and genotypic investigation. Objective 2 will be achieved by in vitro experiments using intestinal epithelial cell lines, primary intestinal epithelial cells derived from mice, and murine and human dendritic cells. Campylobacter strains will be incubated with these cells, and microarray technology will be used to identify genes involved in invasion. Objective 3 will be achieved using novel in vitro bacteria-epithelial cell-DC co-culture systems to determine if infection of intestinal epithelial cells elicits DC responses and can recruit them to epithelial cells. In addition, state-of-the-art live cell imaging will be used to establish routes of epithelial cell invasion. Combined, these three objectives will give new insights into the mechanisms human pathogens use to cause intestinal disease.

Publications

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