Award details

Integrated Biology of the GI Tract

Reference	BBS/E/F/00044446
Principal Investigator / Supervisor	Professor Simon Carding
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	4,316,452
Status	Current
Type	Institute Project
Start date	01/04/2010
End date	31/03/2018
Duration	95 months

Abstract

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 maintaining barrier function and crosstalk with the microbiota and mucosal immune cells and what impact they have on host defence and metabolism. 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 several barrier functions, such as tight junctions, anti-microbial protein secretion by IECs and microbiota components in response to the pathogen S. Typhimurium, selection of the predominant microbiota species and their metabolic activities that act as a colonisation defense against foreign microbes. 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.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Diet and Health, Immunology, Microbial Food Safety, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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