Studentship: What is the impact of mucin degradation in inflammatory bowel diseases

Lead Research Organisation: Institute of Food Research
Department Name: Contracts

Abstract

Inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis result from inappropriate activation of the gastrointestinal (GI) mucosal immune system by the intestinal microbiota. The GI tract is covered by a protective layer of mucus which large glycoprotein mucins constitute the main structural component. The numerous mucin O-glycans not only serve as nutrients for the bacteria but also as attachment sites and, as such, probably contribute to the selection of the species-specific colon flora. Alterations of the mucus layer through changes in mucin glycosylation and/or mucin expression/secretion are often associated with IBD. These changes could result in abnormal interaction between the host and the microbes leading to inflammation. However the molecular mechanisms are currently unknown.
The aim of the project is to relate mucin glycosylation changes to prevalence of mucolytic bacteria in human mucus samples from IBD patients and loss of barrier function in humans.
In objective 1, we will identify changes in mucin glycosylation by lectin mapping of mucins purified from mucosal lavage, using composite gels and force spectroscopy and by mass spectrometry to define the size and the shape of the epitopes.
In objective 2, we will determine changes in mucus-associated bacteria composition by qPCR and next-generation sequencing in collaboration with TGAC.
In objective 3, we will investigate the molecular mechanisms underlying the relationship between mucin glycan alteration (objective 1) and dysbiosis (objective 2) using engineered mice defective in mucin glycosylation following dextran sulphate sodium (DSS)-colitis treatment.
In addition to improving our understanding of disease etiology, this project will help refine diagnostic and monitoring tools for IBD.

Publications

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