Characterising extreme innate immune response phenotypes informative for disease using a functional genomics approach

This research aims to identify people who show extreme responses to lipopolysaccharide (a component of bacterial cell walls) or interferon-gamma (a chemical signalling molecule associated with infection and inflammation) when used to activate white blood cells called monocytes.

The hypothesis is that genetic factors determine such differences between people. We hope to identify specific genes that are affected by having particular genetic variants and the functional consequences. Such information is very helpful for drug discovery. It provides information about the likely consequences of using a particular drug before large financial investments are made. We will analyse data from large existing cohorts of healthy volunteers who have donated blood samples. We will use a model system based on stem cells to generate the cell types of interest and then use new tools for editing the genome using an accurate cut and paste method so that we can test the effects of making a genetic change.

We will work with experts in drug discovery to make sure that our results aid drug development. The work will help patients with different diseases associated with dysregulated immune function including sepsis.