Project Reference: TRG27-MED-AF1

Project title: Defining the rules of bacterial mutagenesis

Project outline

The generation of mutations is vital for bacteria as it introduces genetic diversity upon which natural selection operates. We have found that bacterial mutations are driven by intrinsic biological processes encoded by the bacterium and by extrinsic lifestyle-associated mutagen exposures. Each process leaves a distinct mutational signature within bacterial genomes. Thus, by characterising mutational signatures, we can define intrinsic and extrinsic mutational processes, and thereby infer active biological processes and major ecological niches. In this project, the student will apply computational analyses across large datasets of bacterial genomes to define the rules of bacterial mutagenesis and experimentally validate these conclusions.

The student will initially examine intrinsic mutational signatures by comparing mutational patterns within bacterial species. They will infer lineages where signatures change and test for associated genes and mutations. Identification of these signatures may reveal active biological pathways.

Next, they will extract extrinsic host-associated signatures by comparing mutational patterns across independent host jumps in multi-host bacteria such as Escherichia coli. Application of these signatures may reveal major hosts and inter-host movement dynamics.

Finally, as signatures provide mutational fuel for adaptation, they will examine whether variation in intrinsic and extrinsic signatures may assist or constrain the ability of bacteria to adapt to new niches or acquire antimicrobial resistance (AMR). They will test whether individual mutational processes or their combinations influence the likelihood of acquiring known sets of pathoadaptive and AMR mutations within distinct genetic backgrounds. This will reveal how specific combinations of mutagens and genetic backgrounds influence adaptation.

This project will identify the processes underlying bacterial mutagenesis, revealing new insights into microbial biology, evolution and ecology.

Principal Supervisor

Professor Andres Floto

Email address: arf27@cam.ac.uk

Department / Partner Institute: Medicine

Website: https://www.hlri.cam.ac.uk/staff/professor-andres-floto

BBSRC strategic theme

Understanding the rules of life