Context-dependent acquisition of antibiotic resistance mechanisms, NERC GW4, PhD in Medical Studies studentship. Ref: 3335
About the award
Location: College of Medicine and Health, University of Exeter, ESI Building, Penryn Campus, TR10 9FE
This project is one of a number that are in competition for funding from the NERC Great Western Four+ Doctoral Training Partnership (GW4+ DTP). The GW4+ DTP consists of the Great Western Four alliance of the University of Bath, University of Bristol, Cardiff University and the University of Exeter plus five Research Organisation partners: British Antarctic Survey, British Geological Survey, Centre for Ecology and Hydrology, the Natural History Museum and Plymouth Marine Laboratory. The partnership aims to provide a broad training in earth and environmental sciences, designed to train tomorrow’s leaders in earth and environmental science. For further details about the programme please see http://nercgw4plus.ac.uk/
For eligible successful applicants, the studentships comprises:
- An index-linked stipend for 3.5 years (currently £14,777 p.a. for 2018/19);
- Payment of university tuition fees;
- A research budget of £11,000 for an international conference, lab, field and research expenses;
- A training budget of £4,000 for specialist training courses and expenses.
Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award but no stipend. Applicants who are classed as International for tuition fee purposes are not eligible for funding.
The dramatic increase in antimicrobial resistance (AMR) forms a global challenge to public health. It is increasingly understood that the natural environment plays a key role in AMR evolution. Pharmaceutical residues and other pollutants in the environment such as metals can select for AMR. Moreover, largescale mixing of human-associated- and environmental bacteria can promote the exchange of resistance genes between strains, providing the genetic substrate for selection. Recent work suggests that such horizontal gene transfer might occur at the same rate as mutation but the relative importance of these two fundamentally distinct genetic mechanisms in generating AMR is not known. In this PhD project, we will design experiments to quantify and compare the prevalence of point mutations versus horizontal gene transfer events in generating resistance. Using flow cytometry and genome sequencing, we will measure the type and rate of genetic change under different realistic pollution scenarios. These data will provide fundamental data on bacterial genome evolution but also provide a scientific basis for pollution management.
Project Aims and Methods
The main aim is to combine antibiotic selection with whole-genome re-sequencing in a bacterial pathogen to identify the prevalence of distinct genetic mechanisms (horizontal gene transfer versus (vertical) point mutations) responsible for resistance. Specifically:
1. Antibiotic selection takes place in a continuum from high therapeutic concentrations down to much lower concentrations in the environment. As the costs of AMR mutations are assumed to be generally lower than the cost of carriage of introduced genes, it is hypothesized that the latter type of resistance evolution is more prevalent under higher antibiotic concentrations. We will vary antibiotic concentrations to alter the cost of resistance enabling us to measure the prevalence of mutation-based relative to horizontal gene transfer-based AMR.
2. The uptake of genes is crucially dependent on access to community diversity. Bacteria usually do not live in isolation but are embedded in complex microbiomes. We will test whether resistance evolution via lateral gene transfer is promoted in more diverse microbiomes relative to mutation by varying species diversity in experimental microcosms.
The student will be encouraged to co-develop experiments and analyses.
The student will work in state-of-the-art microbiology labs at the ESI building at the University of Exeter’s Penryn campus where MV, AB and WGs groups are based. Having three local supervisors and their group members will allow efficient knowledge transfer and training in a wide range of skills, including microbiology, genomics and statistics. EFs group is based in the Milner Centre for Evolution at the university of Bath with >20 PI’s in big data science, genomics and informatics which the student will have the opportunity to visit in addition to contact via email and skype. MV and WG are part of the European Centre for Environment and Human Health (ECEHH) which has a mission to disseminate its research via the distribution of videos, interviews and press releases from which the project and student can greatly benefit. MV and WG have contributed to a Wellcome Trust-funded exhibition on gut microbiomes “Invisible You” at the Eden Project providing further opportunities to engage with the public. The student will be encouraged to participate in the wide range of professional development opportunities available at the University of Exeter (http://as.exeter.ac.uk/rdp/researchstaff/) to further career development.
References / Background reading list
Murray, A., Zhang, L., Yin, X., Zhang, T., Buckling, A., Snape, J. and Gaze, W., 2018. Novel insights into selection for antibiotic resistance in complex microbial communities. bioRxiv, p.323634.
Richardson, E.J., Bacigalupe, R., Harrison, E.M., Weinert, L.A., Lycett, S., Vrieling, M., Robb, K., Hoskisson, P.A., Holden, M.T., Feil, E.J. and Paterson, G.K., 2018. Gene exchange drives the ecological success of a multi-host bacterial pathogen. Nature ecology & evolution, 2(9), p.1468.
Vos, M., Hesselman, M. C., te Beek, T. A., van Passel, M. W., & Eyre-Walker, A. (2015). Rates of lateral gene transfer in prokaryotes: high but why? Trends in microbiology, 23(10), 598-605.
Wielgoss, S., Didelot, X., Chaudhuri, R. R., Liu, X., Weedall, G. D., Velicer, G. J., & Vos, M. (2016). A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus. The ISME journal.
Wellington, E.M., Boxall, A.B., Cross, P., Feil, E.J., Gaze, W.H., Hawkey, P.M., Johnson-Rollings, A.S., Jones, D.L., Lee, N.M., Otten, W. and Thomas, C.M., 2013. The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria. The Lancet infectious diseases, 13(2), pp.155-165.
Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree. Applicants with a minimum of Upper Second Class degree and significant relevant non-academic experience are encouraged to apply.
We are looking for a candidate that is willing to engage in wetlab- (experimental evolution, molecular microbiology) and drylab- (genomics, bioinformatics) work. Previous experience in these fields would be advantageous but is not strictly required.
All applicants would need to meet our English language requirements by the start of the project http://www.exeter.ac.uk/postgraduate/apply/english/.
How to apply
In the application process you will be asked to upload several documents. Please note our preferred format is PDF, each file named with your surname and the name of the document, eg. “Smith – CV.pdf”, “Smith – Cover Letter.pdf”, “Smith – Transcript.pdf”.
- Letter of application outlining your academic interests, prior research experience and reasons for wishing to undertake the project.
- Transcript(s) giving full details of subjects studied and grades/marks obtained. This should be an interim transcript if you are still studying.
- If you are not a national of a majority English-speaking country you will need to submit evidence of your current proficiency in English.
- Two References (applicants are recommended to have a third academic referee, if the two academic referees are within the same department/school).
If you do not upload your references when submitting your application, it is your responsibility to ensure that your two referees email their references to firstname.lastname@example.org, as we will not make requests for references directly; you must either upload them with your application or arrange for them to be submitted by 29 April 2019.
Please note: References should be submitted to us directly in the form of a letter. Referees must email their references to us from their institutional email accounts. We cannot accept references from personal/private email accounts, unless it is a scanned document on institutional headed paper and signed by the referee.
All application documents must be submitted in English. Certified translated copies of academic qualifications must also be provided.
The closing date for applications is midnight on 29 April 2019. Interviews will be held week commencing 20 May 2019.
If you have any general enquiries about the application process please email email@example.com. Project-specific queries should be directed to the supervisor.
During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates. These are not limited to, but may include disclosures to:
- the selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from one or more other HEIs;
- administrative staff at one or more other HEIs participating in the relevant programme.
Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.
|Application deadline:||29th April 2019|
|Value:||£14,777 per annum for 2018-19|
|Duration of award:||per year|
|Contact: PGR Enquiriesfirstname.lastname@example.org|