Translation of Scottish macrophage-associated IBD immunopathotypes in Canadian patient cohorts.

"MRC:HannahMoanaBaer:MR/N013166/1"

Scotland and Canada are the two nations with the highest incidence of inflammatory bowel disease (IBD) world-wide and, therefore, have a big requirement for more in-depth research on its disease mechanisms to create more potent therapies. Patients suffering from IBD have chronic inflammation in their intestines, which can be life-threatening in very severe cases.

Currently a large percentage of IBD patients does not respond to front-line treatments, which leaves bowel-removing surgery as last resort for many affected. Scientist world-wide do not know what causes this specific group of individuals, so called non-responders, to maintain inflammation during treatment.

Macrophages are a type of immune cell that monitor our tissues for potential unwanted intruders. They substantially contribute to tissue inflammation in IBD, making them a very common and useful target in anti-inflammatory therapies. During inflammation in IBD, immune cells attack the epithelium, the layer of skin that makes up the lining of our intestines.

One of the main aims of IBD treatments is to achieve full healing of the epithelial layer in our intestines after an immune attack. It is therefore of at-most importance to understand the interaction between immune cells such as macrophages and gut skin cells to reach satisfying treatment results. Previous evidence based on computational analyses of a Scottish IBD cohort predicted that the nature of interaction between intestinal macrophages and the gut epithelium in IBD can identify patients that are more likely to respond to front-line treatments.

During my placement at the University of British Columbia I will have the rare opportunity to learn a unique technique that isolates and grows macrophages and gut skin cells which will allow me to study interaction. I will look at characteristics of both cells in different patients with IBD under a selection of conditions simulating different scenarios of inflammation.

I can study the composition individual cells with a selection of techniques that uses fluorescent or similar signals to detect the levels of specific proteins which define different cellular states. I can also measure the rate by which specific parts of our DNA are transcribed more in the cells than others to see whether different conditions have diverse effects on gene expression.

This project will make great advances in understanding macrophage and gut skin cell interaction in disease and provide a basis for new therapeutic treatment targets.