Equitable multi-ancestry genomics to identify and validate therapeutic targets in severe infection

Project Summary:

Severe infections - including sepsis, pneumonia, and bloodstream infections - kill more than one in five people worldwide. Despite this, few new treatments outside antimicrobials have been developed, despite >30 years of research on novel compounds. One solution to this is genetics, which has been instrumental in drug development outside infection, and drove the identification of key drug targets for COVID-19 that are currently licenced today. This award will support a collaboration between Bristol and McGill University, Montreal, to build an international multi-ancestry infection genomics network. By combining clinical databases and genetic resources we will identify genetic variants that causally protect against severe infection. We will develop two major grant applications: a Wellcome Discovery Award establishing a multi-ancestry genomics consortium, and an MRC Experimental Medicine bid to test two genetically-identified drug targets - IL6R blockade and alpha-1-antitrypsin augmentation in patients with sepsis. Both of these targets were identified by us.

Visitor Biography:

Dr. Guillaume Butler-Laporte is an infectious diseases physician and geneticist at McGill University, where his lab uses and develops genetic epidemiology and bioinformatics tools to study infectious diseases and their links to non-infectious conditions. The unifying thread across his work is causal inference: using large-scale genetic data to distinguish correlation from causation and identify treatment targets that are more likely to translate into successful therapies. During COVID-19, he was a key contributor to one of the largest international genomic collaborations ever assembled, helping prioritize candidate treatments during the pandemic. He is now applying these tools to sepsis, a severe infectious condition that kills 11 million people annually.

Butler-Laporte completed his residency in infectious diseases and medical microbiology at McGill, followed by research fellowships in genetic epidemiology at the Lady Davis Institute and the University of Oxford. Alongside his research, he contributes to multiple clinical trials on the treatment of diverse infectious diseases.