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Reconstructing the last 8 years of drug resistance emergence and plasmid dynamics from public health genomic surveillance data of Shigella


   Department of Life Sciences

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  Dr Lauren Cowley  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

The University of Bath is inviting applications for the following PhD project commencing in October 2023.

Overview of the Research:

The diarrheal pathogen Shigella contributes a significant burden of disease globally with over 125 million cases every year. Alarmingly, drug resistant Shigella infections are becoming more prevalent, as resistance genes disseminate widely in the species, making cases harder and harder to treat. The main vehicle for rapid dissemination of resistance genes is plasmids, including the emergence of multi-drug resistant strains with multiple drug resistance genes located on a plasmid. Previously, intercontinental dissemination of resistance genes on a single plasmid has directly enhanced Shigella outbreaks.

This project will use retrospective sequencing data from the past 8 years of government public health genomic surveillance at UK Health Security Agency (UKHSA) to investigate the emergence, evolution and genomic epidemiology of drug resistance encoding plasmids in clinical samples from the UK. To fully understand the context of resistance genes, we usually require long read sequencing that can resolve highly repetitive regions such as plasmids. However, novel methods that use long-read sequenced reference plasmids to piece together short read sequences can reconstruct a partial image of the plasmid repertoire of short read sequenced strains. Over the course of this project, we will develop methods to systematically piece together and identify characterized reference plasmids in the retrospective dataset and use this information to reconstruct drug resistance plasmid emergence and evolution in relation to the epidemiology of Shigella outbreaks in the UK.

The student will benefit from a supervisory team based in both academia and government public health and will be given the opportunity to spend significant time at the University of Liverpool and UKHSA (subject to formal agreement) as well as the University of Bath over the course of the PhD. 

Project keywords: plasmids, antimicrobial resistance, Shigella, evolution, microbiology.

Candidate Requirements:

Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree (or the equivalent) in a relevant subject. A master’s level qualification would also be advantageous.

Non-UK applicants must meet our English language entry requirement.

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to Dr Lauren Cowley on email address [Email Address Removed].

Formal applications should be submitted via the University of Bath’s online application form for a PhD in Biology prior to the application deadline of Sunday 22 January 2023.

More information about applying for a PhD at Bath may be found on our website.

Funding Eligibility:

To be eligible for funding, you must qualify as a Home student. The eligibility criteria for Home fee status are detailed and too complex to be summarised here in full; however, as a general guide, the following applicants will normally qualify subject to meeting residency requirements: UK and Irish nationals (living in the UK or EEA/Switzerland), those with Indefinite Leave to Remain and EU nationals with pre-settled or settled status in the UK under the EU Settlement Scheme. This is not intended to be an exhaustive list. Additional information may be found on our fee status guidance webpage, on the GOV.UK website and on the UKCISA website.

Exceptional Overseas students (e.g. with a UK Master’s Distinction or international equivalent and relevant research experience), who are interested in this project, should contact the lead supervisor in the first instance to discuss the possibility of applying for supplementary funding.

Equality, Diversity and Inclusion:

We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups.

If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.


Funding Notes

A studentship includes Home tuition fees, a stipend (£17,668 per annum, 2022/23 rate) and research/training expenses (£1,000 per annum) for up to 3.5 years. Eligibility criteria apply – see Funding Eligibility section above.

References

1. Locke RK, Greig DR, Jenkins C, Dallman TJ, Cowley LA. Acquisition and loss of CTX-M plasmids in Shigella species associated with MSM transmission in the UK. Microb Genom. 2021 Aug;7(8):000644. doi: 10.1099/mgen.0.000644. PMID: 34427554; PMCID: PMC8549364.
2. Baker KS, Dallman TJ, Ashton PM, Day M, Hughes G, Crook PD, Gilbart VL, Zittermann S, Allen VG, Howden BP, Tomita T, Valcanis M, Harris SR, Connor TR, Sintchenko V, Howard P, Brown JD, Petty NK, Gouali M, Thanh DP, Keddy KH, Smith AM, Talukder KA, Faruque SM, Parkhill J, Baker S, Weill FX, Jenkins C, Thomson NR. Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study. Lancet Infect Dis. 2015 Aug;15(8):913-21. doi: 10.1016/S1473-3099(15)00002-X. Epub 2015 Apr 27. PMID: 25936611.

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