Investigating mechanisms of extra-cellular matrix remodelling and fibrosis in the gastrointestinal tract

This Investigating mechanisms of extra-cellular matrix remodelling and fibrosis in the gastrointestinal tract project is offered at University of Dundee.

This Investigating mechanisms of extra-cellular matrix remodelling and fibrosis in the gastrointestinal tract Investigating mechanisms of extra-cellular matrix remodelling and fibrosis in the gastrointestinal tract project at University of Dundee University of Dundee will aim to create and characterise a novel experimental model of epithelial-mesenchymal transition (EMT) as a key process involved in gastrointestinal fibrosis, using human tissue derived epithelial organoid models, assess the impact on key pro-fibrotic mediators on this process and explore the interactions with the gut microbiota.

Context

Inflammatory bowel diseases, such as Crohn’s disease, are increasing in prevalence globally. These are caused by chronic inflammation in the gut, there is no cure and medications are not effective for all. In Crohn’s disease, a narrowing of the bowel (termed a stricture) can develop due to the formation of scar tissue in the gut wall due to fibrosis. Approximately one third of people with Crohn’s disease will develop narrowing of the gut, leading to obstruction. This requires an operation to remove the narrowed area. Scar tissue returns in other areas of the gut in many patients.

The student will utilise a large biobank of archival paraffin embedded fibrostenotic Crohn’s disease surgical resection tissue to identify an epithelial and stromal signature associated with recurrent fibrosis using a variety of techniques such as

• immmunohistochemistry

• transcriptomics

• multiplex cell phenotyping