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  Temperate bacteriophages and Antimicrobial Resistance (AMR) (Ref: SF20/APP/SMITH2)


   Faculty of Health and Life Sciences

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  Prof Darren Smith  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Bacterial genomes are studded with prophage regions, some that can be stimulated to produce active phages that horizontally transfer their genomes between related bacterial species. They have a highly ordered conservation of genes that is required for their life cycle including infection, proliferation and release. Importantly for this study they also carry genes of accessory function, sometimes known as cargo genes that can offer positive selection for the bacteriophage or lysogen in that environment. We have previously demonstrated the impact of the well-characterised Shiga toxin-prophage ϕ24B on its Escherichia coli host MC1061. As a lysogen, the prophage alters the bacterial physiology by increasing the rates of respiration and cell proliferation. Phage-mediated control of the E. coli biotin and fatty acid synthesis pathway are rate limiting to cell growth. Through ϕ24B conversion the lysogen also gains increased antimicrobial tolerance to chloroxylenol and 8-hydroxyquinoline. Distinct metabolite profiles discriminate between MC1061 and the ϕ24B lysogen in standard culture. How temperate bacteriophages play a role in microbial infection and the development of true antimicrobial resistance is not fully understood. We will look at rates of phage mediated conversion to AMR mapping genomic changes in the phage and bacterium to determine patterns of progression to resistant phenotypes.
You will use the latest in omics technologies and learn bioinformatic skills supported by an experienced team. You will learn lab-based methods in handling bacteriophages, their infection and how to characterise and curate bacteriophage genomes. You will learn how to data mine these bacteriophage genomes for specific function and to use molecular methods to determine if these traits are unequivocally functional.

Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
• Applicants cannot apply for this funding if currently engaged in Doctoral study at Northumbria or elsewhere.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed and the reasons you consider yourself suited to the project. Applications that do not include the advert reference (e.g. SF20/…) will not be considered.

Deadline for applications: 1st July for October start, or 1st December for March start
Start Date: October or March
Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality.

Informal enquiries to Dr Darren Smith ([Email Address Removed])

Funding Notes

This project will be self funded – fee bands are available at https://www.northumbria.ac.uk/study-at-northumbria/fees-funding/ . A relevant fee band will be discussed at interview based on project running costs

References

Tariq MA, Everest FLC, Cowley LA, Wright R, Holt GS, Ingram H, Duignan LAM, Nelson A, Lanyon CV, Perry A, Perry JD, Bourke S, Brockhurst MA, Bridge SH, De Soyza A, Smith DL. 2019. Temperate bacteriophages from chronic Pseudomonas aeruginosa lung infections show disease-specific changes in host range and modulate antimicrobial susceptibility. mSystems 4:e00191-18. https://doi.org/10.1128/mSystems.00191-18.

Holt, G. S, Lodge, J, McCarthy, A. J, Graham, A.K, Young, G, Bridge, S. H, Brown, A. K, Veses-Garcia, M, Lanyon, C.V, Sails, A, Allison, H. E. and Smith, D. L. (2017) Shigatoxin encoding Bacteriophage φ24 B modulates bacterial metabolism to raise antimicrobial tolerance Nature Scientific Reports 7, 40424; doi: 10.1038/srep40424 (2017).

Smith, Darren, Rooks, David, Fogg, Paul, Darby, Alistair C., Thomson, Nick R., McCarthy, Alan and Allison, Heather (2012) Comparative genomics of Shiga toxin encoding bacteriophages. BMC Genomics, 13 (1). p. 311. ISSN 1471-2164

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