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Ecological and evolutionary drivers of mobile antibiotic resistance


   Department of Biology

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  Prof Craig MacLean  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

This project is part of the DPhil in Biology at the University of Oxford

Antibiotic resistance in pathogenic bacteria (AMR) has emerged as a serious threat to society: resistant infections currently cause 1-5 million deaths per year resistance also has important implications for agriculture and food security. The overarching goal of research in the MacLean lab is to understand the evolutionary and ecological drivers of AMR. Many of the most important antibiotic resistance genes are carried on plasmids that can transfer between bacterial cells by the process of conjugation.

At a very broad scale, it is clear that plasmids have played a key role in AMR by moving resistance genes from environmental and commensal bacterial to pathogens. However, our understanding of the ecological and evolutionary drivers of plasmid mediated AMR remains limited.

The goal of this project will be to address the following questions:

  1. How do plasmids impact the stability of resistance? Resistance genes impose fitness costs, and these costs can lead to the loss of resistance after antibiotic use. This project will test the hypothesis that the ability of plasmids to spread infectiously between bacterial cells makes mobile resistance more stable than chromosomal resistance.
  2. What limits the host range of plasmids? Pathogenic bacteria are embedded in diverse microbiomes, but many plasmids only transfer between closely related strains or species. This project will test the hypothesis that different host strains effectively represent different niches for plasmids, and that trade-offs limit plasmids host range.

This project will investigate these questions using an experimental evolution approach. Populations of the bacterium E.coli carrying plasmids that confer resistance to clinically important antibiotics will be passaged in lab culture medium containing simple bacterial communities for 10s to 100s of generations. This approach will make it possible to simultaneously study the ecological and evolutionary drivers of antibiotic resistance, and to manipulate key variables that are predicted to influence resistance. Genome sequencing will make it possible to study the molecular mechanisms of AMR plasmid evolution. The project will be based in a dynamic and diverse research group that brings together researchers with a wide variety of backgrounds to tackle the problem of AMR.

There will also be good opportunities for collaboration with groups based in the UK (Oxford, Manchester) and Europe(Madrid, Paris, Berlin). This project is motivated by the idea of trying to combine ecological and evolutionary ideas with microbiology and it is ideally suited for ambitious and highly motivated students who want to learn new scientific approaches and apply them to an urgent problem.

This project is part of the Microbiology & Infectious Disease theme in the Department of Biology.

Funding

This project is part of the DPhil in Biology programme, and is not a funded course at the University of Oxford, as such, students are expected to explore options for funding. However, we anticipate being able to offer around 6 full graduate scholarships to incoming DPhil Students in 2023-24

You will be automatically considered for the majority of Oxford scholarships, if you fulfil the eligibility criteria and submit your graduate application by 20 January 2023. Scholarships are awarded on the basis of academic achievement and potential to excel as a DPhil student. 

For further details about searching for funding as a graduate student visit the University’s dedicated Funding pages.

Eligibility

For full entry requirements and eligibility information, please see the main admissions page.

How to apply

The deadline for applications for 2023-2024 entry is midday 20 January 2023. We will continue to accept applications submitted after 20 January 2023, but these late applications will not be considered for scholarship funding.

You can find the admissions portal and further information about eligibility and the DPhil in Biology Programme at the University's graduate admissions page.


References

1. Perspective – The Evolution of Antibiotic Resistance. R.C MacLean and A. San Millan. Science (2019) DOI: 10.1126/science.aax3879
2. Assessing evolutionary risks of resistance for new antimicrobial therapies. M. A. Brockhurst, F. Harrison, J-W. Veening, E. Harrison, G.Blackwell, Z.Iqbal and C. MacLean. Nature Ecology and Evolution (2019) doi: 10.1038/s41559-019-0854-x
3. Integron activity accelerates the evolution of antibiotic resistance. C. Souque, J.A. Escudero* and R.C. MacLean*. eLife (2021) doi: 10.7554/eLife.62474
4. Multicopy plasmids potentiate the evolution of antibiotic resistance in bacteria. A. San Millan, J.A Escudero, D.Gifford, D. Mazel and R.C MacLean Nature Ecology and Evolution (2016) doi:10.1038/s41559-016-0010
5. Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids. A. San Millan, R.Peña-Miller, M. Toll-Riera, Z.Halbert, A.McLean, B.Cooper and R.C MacLean. Nature Communications (2014) 5, doi:10.1038/ncomms6208.

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