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The evolution of antimicrobial resistance in human infections


Faculty of Biology, Medicine and Health

About the Project

Antibiotics are our main defence against bacterial infections, but rising levels of resistance risks rendering antibiotics ineffective. The most effective solution to the AMR crisis would be to prevent resistance from evolving at all. However, we do not yet understand how resistance evolves within human infections, or why resistance evolves in some treated individuals but not in others. A better understanding of what drives between patient variation in the emergence of AMR could help improve the targeting of treatments to minimise resistance evolution, and thus lead to better antibiotic stewardship. In this project, we will combine high-throughput genomic screening of antibiotic resistant bacterial genotypes isolated from human infections together with laboratory evolution experiments to test how changes in the microenvironment of infection sites alter the trajectory of AMR evolution. In particular, we will focus on how key effectors of the inflammatory immune response alter selection for antibiotic resistance in an in vitro model of human lung infection previously developed in our labs (Davies et al. 2017 PNAS 113:8266-8271). This PhD project will provide broad training in microbiology, evolutionary biology, genomics and bioinformatics, experimental design and statistics.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in microbial evolution or with an interest in the evolution of antimicrobial resistance are strongly encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Microbiology.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

DR Gifford, V Furió, A Papkou, T Vogwill, A Oliver, RC MacLean (2018) Identifying and exploiting genes that potentiate the evolution of antibiotic resistance, Nature Ecology & Evolution, doi: 10.1038/s41559-018-0547-x.

Gifford, D.R., Krašovec, R., Aston, E., Belavkin, R.V., Channon, A. and Knight, C.G. (2018) Environmental pleiotropy and demographic history direct adaptation under antibiotic selection. Heredity, 121, 438-448. http://doi.org/ctm6

Bottery M, Wood AJ, Brockhurst MA. Adaptive modulation of antibiotic resistance via intragenomic coevolution. Nature Ecology and Evolution. 2017. 1:1364-1369.

Davies EV, James C, Williams D, O’Brien S, Fothergill J, Haldenby S, Paterson S, Winstanley C, Brockhurst MA. Temperate phages both mediate and drive adaptive evolution in pathogen biofilms. Proceedings of the National Academy of Sciences USA. 2016. 113:8266-8271.

Williams D, Evans B, Haldenby S, Walshaw MJ, Brockhurst MA, Winstanley C, Paterson S. Divergent, coexisting Pseudomonas aeruginosa lineages in chronic cystic fibrosis lung infections. American Journal of Respiratory and Critical Care Medicine. 2015. 191:775-85.

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