Integrated Biology of the GI Tract
Research Summary
Our research is in three areas representing the three major components of the GI Tract; the bacteria (microbiota) that reside in the gut, the epithelial cells lining the gut that act as a barrier to invasive organisms, and the immune system that protects against infection. Our overarching aim is to understand how these three components interact to preserve gut health, which will help explain how and why these interactions go wrong in chronic inflammatory disorders such as food allergy, inflammatory bowel disease and colorectal cancer.
Gut Immunity
Led by: Simon Carding
Our primary objectives are to determine the molecular basis of the interactions between intestinal epithelial cells and the microbiota and define what the outcome of these interactions is for host immune responses, and if epithelial cells can distinguish between different microbiota species. Investigating the influence epithelia-associated immune cells have on anti-microbial defences and anti-microbial protein production by intestinal Paneth cells is a specific interest. This work will be complemented by studies on microbe-epithelial cell interactions and their outcomes in the human colon using a unique human crypt culture model system in collaboration with the group at UEA that developed this system. The important objectives are to establish the role that epithelial cells and dendritic cells play in sampling and responding to enteric antigens in different regions of the GIT, and to identify the antigen presenting cell that reacts with food antigens and triggers local food hypersensitivity reactions. Intravital multi-photon microscopy will be used to image and track these interactions.
The Gut Epithelium
Led by: Nigel Belshaw
We are focused on identifying the mechanisms that maintain mucosal integrity and barrier function as well as environmental factors, including sub-optimal nutrition and microbial agents that interact with the epithelium and the impact that age-related loss of crypt homeostasis has on epithelial homeostasis. Specific interests are defining the mechanisms that regulate the formation and maintenance of intercellular epithelial tight junction complexes that are integral to epithelial barrier function. The effects of metabolic stress on epithelial cytoskeletal adaptation and colonic crypt homeostasis is another area of interest, as are studies investigating the mechanisms of age-related CGI methylation and the impact diet, metabolism and the microbiota have on this process. In addition, the impact of dietary fats and fish-derived polyunsaturated fatty acids on colonic epithelial homeostasis will also be investigated.
The Microbiota
Led by: Nathalie Juge
We are concerned with defining the extent and diversity of the metabolic activity of the microbiota and in establishing a set of characterised metabolic pathways. How colonic bacteria, and in particular those that reside within the mucus layer that coats the intestinal epithelium, regulate and modulate the development and maintenance of the mucin barrier will be investigated. An ambition is to develop, as an enabling technology, a model microbiota that is representative of the human colonic microbiota. This new technology builds on the strong track record the IFR has in molecular biology of commensal bacteria and the successful development and use of in vitro models of the human colon (Dynamic Gastric Model). The model microbiota will provide us with a powerful tool for investigating the function of the GIT microbiota at the single species and community level and the nature of its interaction with the host. It will also become an integral part of studies investigating the extent, diversity and function of metabolic diversity in the microbiota.
Fax: +44(0)1603 507723 
