Integrated Biology of the GI Tract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

This project aims to understand the cellular and molecular basis of the host response to antigenic challenge within the gastrointestinal tract as the inability to regulate responses to the microbiota is a causal factor in the development of chronic inflammation. The hypothesis to be tested is that intestinal barrier function is the sum of interactions between the epithelium and local immune cells and that in response to enteric antigens, epithelial cells promote the development of appropriate host responses to harmless versus harmful antigens. The project is split into two main areas: the role of the intestinal epithelium and the role of intestinal immune cells. Investigation into the epithelium focuses on bacterial recognition receptors, Toll-like receptors (TLR) and NOD2, and how they mediate communication between the gut microbiota and the host's intestinal epithelial cells (IEC). Using a novel primary IEC system and knockout mouse models we are investigating the involvement of TLRs and NOD2 in IEC turnover in response to commensal or pathogenic microbes. In addition, tight junction proteins, which are pivotal in the maintenance of the epithelial barrier, and downstream pathways are being investigated in response to pathogenic microbes. In conjunction with the epithelium, intestinal immune cells such as intra-epithelial lymphocytes (iELs) and dendritic cells (DCs) play a part in regulating the host response to microbes. Specifically we are investigating the role of iELs in the regulation of anti-microbial protein secretion by IECs in response to the pathogen S.typhimurium. We are also interested in the communication between the epithelium and the migration/recruitment of DCs to the mucosa and how this plays an important role in the development of colitis. Our experimental approach involves the use of knockout mouse models, siRNA, primary and secondary cell culture with immunofluorescent imaging, qRT-PCR, ELISA, molecular biology and flow cytometry techniques.

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