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

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. There are no medications available to treat or prevent the scar tissue. In order to develop new treatments, we need to understand the biological mechanisms that cause the scar tissue to develop and this will be the focus of this project. 

This project 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. The student will also 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 immunohistochemistry, transcriptomics and multiplex cell phenotyping. Endothelial-mesenchymal transition is also associated with fibrotic processes and the role of this in the gut are not known. This will be assessed in the archival human samples and biologic mechanisms explored in experimental models such as endothelial cell-fibroblast co-culture. This translational science project using human tissue models will offer experience and skills in a wide array of lab methods such as cell culture, organoid advanced cell culture, molecular methods, cell protein expression, immunohistochemistry, digital pathology analysis, immunofluorescence, microscopy, and data analysis.

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Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.