Tackling the complex regulation of individual intestinal cells

Exploring how individual epithelial cells respond to challenges in the gut.

Project Summary.

Led by: Korcsmáros Group

Start date: March 2015

End date: Ongoing

Duration: Ongoing

Grants: UKRI / BBSRC

All animals, including humans, are ecosystems living together with microbial partners which are often essential for the development and function of organs. While we have substantial knowledge of how human cells are communicating with each other to affect cellular processes such as differentiation and metabolism, our understanding is far more limited on how similar signals produced by microbes affect host processes.

Using multidisciplinary approaches based on experimental data and computational tools, we are investigating key microbial influences on epithelial cells in healthy and diseased states of the digestive system.

For that we implement cutting-edge single cell sorting/RNA sequencing approaches on intestinal cell type-specific individual cells challenged with defined microbes. Using specific gene deletion mutants of these microbes allows us to validate the specific impact microbes have on host cellular processes in a cell type-specific manner.

Impact statement.

Monitoring how the response of individual intestinal cells varies within each cell type upon challenge with either other host cells or with microbes will define subpopulation cell behaviour and therefore increase the resolution at which we might understand what drives the overall response of intestinal tissue.

The regulatory network we are establishing within cells, between cells, between cell types and in response to microbial influence will contribute to identifying regulatory nodes in cellular pathways where intervention could be tested to restore epithelial homeostasis when it is perturbed or to reduce the impact of these alterations.