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Conflicts in the pangenome: integrating evolutionary and structural microbiology to understand plasmid costs and genome defence

Project Description

Billions of bacteria around the world are currently exchanging genes, undergoing a powerful evolutionary process called horizontal gene transfer (HGT). The consequences are profound — HGT enables bacteria to degrade new food sources, resist antibiotic treatment, decontaminated polluted land, or interact with plants and animals. However, openness to new genes can make bacteria more vulnerable to incoming DNA that is parasitic or even lethal, e.g. in the form of bacteriophage. A diverse array of ‘genome defences’ have evolved to defend against such events, some of which (CRISPR and restriction endonucleases) have proved useful not only for bacteria but also for biotechnology. Conflicts between bacteria, bacteriophage, and other vectors of HGT such as plasmids are likely to play a major role in determining genome content and hence bacterial evolution, but their molecular bases and how they drive evolutionary patterns are unclear.

This multi-disciplinary, cross-institutional project combines evolutionary microbiology with structural and molecular biology to ask: “what are the tradeoffs between HGT and genome defence?” Previous work by our groups has identified a family of uncharacterised proteins in E. coli and Pseudomonas that seem to act both as barriers to HGT and in defence against bacteriophages. Using diverse approaches, the student will map this uncharted frontier in the struggle between bacteria and their mobile genetic elements by:
1. Characterising the effects of these proteins on bacterial fitness and evolution, using reverse genetics, gene expression analysis, and competition experiments;
2. Investigating the distribution of these proteins across different species of bacteria;
3. Determining the molecular bases of interactions using structural/molecular biology approaches including X-ray crystallography and DNA-binding assays.

Employing a broad range of techniques, this project will inculcate innovative, integrative biological thinking in the student who will also receive expert laboratory training across three Universities (Liverpool, Sheffield, Durham) in evolutionary microbiology, structural biology, molecular biology, and bioinformatics. The student will also receive training in activities such as scientific writing, presentation, literature reviewing, and statistical analysis, developing skills that will place them in an excellent position for a future scientific career.

Applicants should generally have an upper second or first class degree. Background in relevant subjects would be helpful, but more important are enthusiasm for evolution/microbiology, self-motivation, and the drive to develop an independent research project. Please get in touch by email if you have any questions about this project or your application — informal pre-application enquiries are strongly encouraged.

Applications should be made by emailing with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to . A blank copy of this form can be found at:
Informal enquiries may be made to

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.


Extremely fast amelioration of plasmid fitness costs by multiple functionally diverse pathways. 2019. Microbiology. doi: 10.1099/mic.0.000862

Conflicting selection alters the trajectory of molecular evolution in a tripartite bacteria-plasmid-phage interaction. 2017. Molecular Ecology, 26(10), 2757–2764. doi: 10.1111/mec.14080

The Ecology and Evolution of Pangenomes. 2019. Current Biology, 29(20), R1094–R1103. doi: 10.1016/j.cub.2019.08.012

The evolution of plasmid stability: Are infectious transmission and compensatory evolution competing evolutionary trajectories? 2017. Plasmid, 91, 90–95. doi: 10.1016/j.plasmid.2017.04.003

Source-sink plasmid transfer dynamics maintain gene mobility in soil bacterial communities. 2016. Proceedings of the National Academy of Sciences of the United States of America, 113(29), 8260–8265. doi: 10.1073/pnas.1600974113

Parallel compensatory evolution stabilizes plasmids across the parasitism-mutualism continuum. 2015. Current Biology: CB, 25(15), 2034–2039. doi: 10.1016/j.cub.2015.06.024

Bacteriophages limit the existence conditions for conjugative plasmids. 2015. mBio, 6(3), e00586. doi: 10.1128/mBio.00586-15

Evolution of Pectobacterium bacteriophage ΦM1 to escape two bifunctional Type III toxin-antitoxin and abortive infection systems through mutations in a single viral gene (2017) Applied and Environmental Microbiology 83(8): e03229-16

Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot (2013) Proceedings of the National Academy of Sciences of the United States of America 110(3): E241-9

A processed non-coding RNA regulates an altruistic bacterial antiviral system (2011) Nature Structural and Molecular Biology 18(2): 185-190

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