(WIS) Targetting unappreciated gut macrophage populations to treat inflammatory bowel diseases (IBD)

Inflammatory bowel diseases (IBD) are severe chronic gastrointestinal disorders that affect over half a million people in the UK and are dramatically increasing in prevalence. Although broad immune suppressants can limit inflammation, many patients become resistant to treatment and require surgical intervention to remove large parts of their intestine. It is crucial that we understand the cellular and molecular pathways underlying gut inflammation to identify novel therapeutic pathways for treatment of this life-limiting disease.

Macrophages are vital immune cells in the gut that are important in IBD as they play diverse, and seemingly conflicting roles, in disease pathogenesis, promoting inflammation but also supporting tissue remodelling and resolution. The mechanisms by which such diverse functions can be instructed are still poorly understood but a high degree of specialisation by distinct macrophage populations is on important factor.

The Grainger Group at The University of Manchester has recently identified a novel population of gut macrophages that potentially have important roles in gastrointestinal inflammation. Working together with The Jung Group at Weizmann Institute of Science, who are world leaders in macrophage development, we intend to generate tools to study this unappreciated population of gut macrophages.

Overall, the aim of this project is to better understand the functions of specific macrophage populations in the gut in health and during inflammation. To achieve this, the project will utilise: sophisticated mouse models, in vitro assays and bioinformatics approaches to mine already available murine and human datasets.

Given the interdisciplinary nature of this project undertaking these studies will lead to training in many cutting-edge cellular and molecular immunology techniques including: in vivo models of inflammation, in vitro culture of murine immune cells, multicolour flow-cytometry and genome-wide transcriptional profiling. Training in bioinformatics required to analyse generated datasets will also be provided. Ultimately, this project’s goal is to inform development of novel therapeutics for IBD. Moreover, data generated will improve our current understanding of macrophage biology, providing insight into a plethora of disorders in which aberrant macrophage function is implicated; ranging from obesity to cancer.

Entry Requirements:
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.