Project Reference: TRG27-GEN-AH2

Project title: Viral Counter-Defence in Living Cells: From Molecular Mechanism to Infection Outcome

Project outline

Bacteria and the viruses that infect them are locked in a continual evolutionary race: bacteria evolve defence systems, while phages evolve counter-defences that disable them. Yet identifying a defence and its inhibitor does not tell us whether infection will succeed inside a living cell, where the timing and abundance of both systems, and the physiological state of the host, can vary dramatically.

This project will ask what determines whether a viral counter-defence wins this race against bacterial immunity. Using DNA-mimicking phage proteins such as T7 Ocr and related counter-defence systems as tractable models, the student will combine genetics, molecular and computational approaches with quantitative single-cell infection experiments. Natural and engineered counter-defences will be used to test how their molecular properties, expression timing and abundance interact with bacterial defence strength and host physiology to determine infection outcome.

Mathematical and computational analysis will identify combinations of defence, counter-defence and cellular state that allow infection to proceed, while experiments will test whether the same molecular mechanism succeeds equally well across heterogeneous bacterial populations. The project will then ask how these single-cell outcomes translate into phage fitness and shape the evolution of counter-defence strategies.

By connecting molecular mechanisms of viral counter-defence to infection dynamics in living cells, the project aims to uncover general principles governing host–virus races. Ultimately, understanding what makes counter-defences robust across physiological states could help guide the selection or engineering of phages that remain effective against defended bacterial populations.

Principal Supervisor

Dr Antoine Hocher

Email address: ah2368@cam.ac.uk

Department / Partner Institute: Genetics

Website: https://www.gen.cam.ac.uk/people/antoine-hocher

BBSRC strategic theme

Understanding the rules of life