Project Reference: TRG27-GEN-FJ1

Project title: What happens when a virus meets a new host? A 76-year natural experiment

Project outline

In 1950 myxoma virus was released into rabbit populatio as a biocontrol agent. It killed 99.8% of the rabbits it infected, one of the most lethal epidemics ever recorded. Within three years the virus had become less deadly, and over the following decades it evolved again — this time gaining the ability to potently suppres the rabbit immune system. Rabbits, meanwhile, evolved resistance. Because the release was deliberate and documented, and because virologists have collected the virus ever since, we have something no other system offers: a collection of viruses spanning 76 years of evolution, many with the disease caused measured.

This project asks what actually changed. Viruses evolve at the level of DNA, but what matters for disease is what their proteins do inside the host cell, and that is invisible in a genome sequence. You will infect cells with viruses from across the archive and use mass spectrometry to measure how each remodels the rabbit proteome. The central question is whether viruses evolving independently in Britain and Australia arrived at the same solution, and whether we can identify the viral genes responsible.

You will then use reverse genetics to build viruses carrying particular ancestral or evolved versions of candidate genes, and ask whether swapping a single gene reproduces the change seen in nature.

The rules that emerge should apply whenever a virus jumps into a new host, a problem that matters across human, livestock and wildlife disease.

The project combines evolutionary biology with cutting-edge proteomics and you will be trained in both. You will be based in the Department of Genetics (Frank Jiggins) and Cambridge Institute for Medical Research (Mike Weekes). No previous experience of proteomics is expected.

Principal Supervisor

Professor Frank Jiggins

Email address: fmj1001@cam.ac.uk

Department / Partner Institute: Genetics

Website: https://www.gen.cam.ac.uk/research-groups/research-groups/jiggins

BBSRC strategic theme

Understanding the rules of life