Investigating the molecular mechanisms of disease using human tissue, genetics and artificial intelligence

This research cluster will tackle the “missing link” between the genome and disease. Our aim is to identify molecules in our bodies that cause disease by looking at how tiny variations in the genome change these molecules in single cells. We will create a unique dataset by reading molecular signals in human cells donated by hundreds of patients, potentially leading to ideas for new, effective drugs. By developing new artificial intelligence tools to analyse this data, we will extract much more knowledge from each cell, from each patient.

Investigating the molecular mechanisms of disease

Building on data from 25 years of genetic research since the sequencing of the human genome, we already know tens of thousands of genetic variants underlying a range of diseases. The “missing link” is the molecular mechanisms that are controlled by these disease-associated genetic variants. If we can find these links, we can find new treatments for disease.

We will examine key molecular events in every single cell in left-over samples donated by hundreds of patients undergoing surgery or other procedures – initially brain, skin, blood and lung samples but rapidly expanding to other tissue types in  future. We will stimulate these cells in numerous different ways in the lab to reveal the molecular events that occur in the body during disease.  And we will create new artificial intelligence methods to read more information from these samples by learning from other experiments.

We have already proven that this can work: we found a genetic variant associated with Covid-19, and showed that a single molecular change in immune cells was controlled by that variant. This molecular mechanism led directly to the discovery of a new, effective drug treatment for Covid-19 which is now used all over the world.

In the Molecular Mechanisms Cluster we hold ourselves to a simple measure of success: the number of disease genes explained.* If we achieve this, we will reveal the fundamental mechanisms underlying a range of diseases, enabling and accelerating development of new and effective treatments.

(* number of disease-associated common genetic variants significantly colocalising with molecular quantitative trait loci.)