Mechanisms of intestinal barrier function in health and inflammation

Supervisor:  Prof Alison Simmons

We have utilized single-cell RNA-sequencing to redefine cell populations within the human intestinal mucosa in health and inflammation such epithelial, stromal, immune and various rare intestinal subsets whose molecular architecture has so far been poorly established. This has revealed new intestinal cell states and suggested novel molecular mechanisms of barrier function and pathways that might be dysregulated in inflammation. In this work selected observations from this data will be explored in depth in in vitro tissue systems and in vivo models to establish new paradigms for innate defense in the intestine. It will be possible to examine the role of the intestinal microbiota in stabilizing these pathways in health or dyregulating these pathways in inflammation. The work will involve use of large scale genetic screens, 3D cell culture systems, in vitro and in vivo imaging and single cell or molecule technologies.

The work will be based at the Weatherall Institute of Molecular Medicine. The lab is multidisciplinary consisting of a mix of scientists, clinicians, bioinformaticians, and a clinical trials team undertaking support studies in experimental medicine with research endoscopy component. Our work is supported with strong collaborations across the campus and with industry giving an opportunity to directly translate relevant findings. 

For further information please contact:

Prof Alison Simmons