The Edinburgh Molecular Mechanisms Cluster

Modern medicine enables doctors to treat diseases better than ever before, but there is still much more to learn. Human genetics can help. Tens of thousands of genes have been found underlying a number of devastating diseases, from Alzheimer's to COVID-19. These genes sometimes gives us clues that can help everyone with that disease, not just people who have particular genes. We have already shown that this works: we found a gene in severe COVID-19 that led directly to a new and effective treatment.

To make the jump from disease gene to treatment, we need better information about what disease genes actually do in the right cell types from the human body, and in conditions that mimic real disease.

Our plan is to set up a system to study how genes work in hard-to-get cell types and conditions. We will use real human samples, donated by our patients, that would otherwise be discarded. We are already able to do this with samples of brain, lung, and skin. To mimic the complicated environment inside a patient even more closely, we will then add a range of different chemicals to the samples and see what happens to the genes, and the cells.

We will share our data quickly with scientists across the world to move medical research and drug development forward. We will build a community of doctors and scientists to help guide us towards the most important and useful gene functions.

Together, our system will give much more information about genes and how they work to make disease better or worse, giving us a chance to find better and more accurate treatments to help more patients.

We will build an open, collaborative molecular quantitative trait loci (molQTL) discovery programme focusing on disease-relevant tissues. The ultimate aim is to translate existing findings from a wide range of genome-wide association studies (GWAS), using molQTL to infer molecular mechanisms of disease, and ultimately identifying effective new therapies. We will achieve this by focusing on disease-relevant tissues and states: in this initial 4-year project, we will use cultured samples of human brain, lung, skin and blood using established systems. Each tissue will be perturbed using a range of 5-10 different stimuli to unmask indicuble gene expression. Our primary metric of success will be the number of disease GWAS loci co-localising with molQTL detected in our work.