Details
Bacteriophage are both the most numerous biological entities on our planet; they are viruses that have evolved to exquisitely target bacterial pathogens with which they have co-evolved. This project aims to use a combined structural (Cryo-EM, electron tomography), biochemical (enzymology), microbiological (phage infections, AMR
assays) and genetic approaches (variant sequencing) to uncover the mechanisms occurring at the bacterial cell surface during phage killing of the multiply drug-resistant pathogen Enterococcus faecium. The work will uncover the fundamental mechanisms at work at this
cross-kingdom viral-bacterial interface and help to pave the way
towards the realization of bacteriophage based therapies to treat
incurable drug-resistant infections.
You will join a thriving microbiology and structural biology community in Sheffield focussing on AMR pathogens and bacteriophage and join a supportive and stimulating intellectual environment. This project will provide a broad training in phage biology, structural biology as well as basic bioinformatics.
The University of Sheffield and the DTP provides bespoke training programmes and has the highest standards of Equality and diversity programmes with its One University pillar.
About the DTP
This studentship is offered as part of the White Rose BBSRC Doctoral Training Partnership (DTP) in Mechanistic Biology, which brings together the research of the world-class molecular and cellular bioscience centres at the White Rose universities of Leeds, Sheffield and York.
Our mission is to train excellent bio-scientists who understand how living systems work
and can innovate to address global challenges, such as the impact of climate change, a healthier old age, sustainable food production, land use and energy production.
What is on offer?
This is a core studentship for entry in October 2024.
Join us and you will receive a 4-year, funded PhD programme of research and skills training, with cross-disciplinary supervision, plus a structured programme of cohort-wide training and networking events. A highlight is the annual symposium, which is planned and delivered by students.
A unique part of your training will be the Professional Internships for PhD Students (PIPS), where you will spend three months at a host organisation of your choosing, gaining experience of work in a professional environment, and acquiring transferable skills that will be beneficial in your future career.
How to apply – Expression of Interest
Students may apply for up to three projects anywhere in the Doctoral Training Partnership (DTP). Applications will be to the DTP centrally, using an online Expression of Interest (EoI). The EoI will include:
§ CV information; not submitted separately
§ Equality, Diversity and Inclusion (EDI) data
§ Names of two referees
Deadline for EoIs is midnight Sunday 7th January 2024.
Submit EoIs using this link: https://leeds.onlinesurveys.ac.uk/white-rose-bbsrc-dtp-expression-of-interest-form
Shortlisted candidates will be required to make formal applications to the Graduate School at each institution, supplying the necessary paperwork.
Interviews will be held either Friday 2nd and Monday 5th to Friday 9th February, or Monday 19th to Friday 23rd and Monday 26th February 2024, in-person at Leeds, Sheffield and York, with a panel representing all 3 Universities. Shortlisted candidates will be notified of a specific time/date to attend. If you have applied for more than one project and are selected for interview, you will be interviewed only once.
Website: https://www.whiterose-mechanisticbiology-dtp.ac.uk/
Funding Notes
Appointed candidates will be fully funded for 4 years:
Tax-free annual stipend at the UKRI rate. The rate for starters in 2023/24 was £18,622. (Rates for 2024/25 starters are not yet available).
UKRI tuition fees – These are paid directly to the host institution.
A Research Training and Support Grant
An allowance for Fieldwork/Conference/Travel
A Professional Internship for PhD Students (PIPS) allowance
Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.
References
1) Alrafaie AM, Stafford GP.(2023) Enterococcal bacteriophage: A survey of the tail associated lysin landscape. Virus Res. 2023 Apr 2;327:199073. doi: 10.1016/j.virusres.2023.199073. Epub 2023 Feb 22. PMID: 36787848; PMCID: PMC10194240.
2) Satur MJ, Urbanowicz PA, Spencer DIR, Rafferty J, Stafford. GP. (2022) Structural and functional characterisation of a stable, broad-specificity multimeric sialidase from the oral pathogen Tannerella forsythia. Biochem J. 2022 Sep 16;479(17):1785-1806.
3) Al-Zubidi, Court EK, Gains AF, Smith RE, Ansbro K, Alrafaie A, Evans C, Murdoch C, Mesnage S, Douglas CWI, Rawlinson A, Stafford GP.Identification of Novel Bacteriophages with Therapeutic Potential That Target Enterococcus faecalis. Infect Immun. 2019 Oct 18;87(11).
4) Court EK, Chaudhuri RR, Kapoore RV, Villa RX, Pandhal J, Biggs CA, Stafford GP. Looking through the FOG: microbiome characterization and lipolytic bacteria isolation from a fatberg site. Microbiology (Reading). 2021 Dec;167(12):001117. doi: 10.1099/mic.0.001117. PMID: 34870579; PMCID: PMC8744997.
1. Wilson JS, Fortier L-C, Fagan RP & Bullough PA (2023)
‘Molecular mechanism of bacteriophage tail contraction-
structure of an S-layer-penetrating bacteriophage.’ BiorXiv doi: https://doi.org/10.1101/2023.08.04.551987
2. Lanzoni-Mangutchi, P, Banerji, O., Wilson, J., Barwinska-Sendra, A., Kirk, J. A., Vaz, F., O’Beirne, S., Baslé, A.; El Omari, K., Wagner, A., Fairweather, N. F., Douce, G. R., Bullough, P. A., Fagan, R. P., Salgado, P. S. ‘Structure and assembly of the S-layer in C. difficile’ Nature Comms. 13 2022) 970.
3. Janganan, T. K., Mullin, N., Dafis-Sagarmendi, A., Brunt, J., Tzokov, S. B., Stringer, S., Moir, A., Chaudhuri, R. R., Fagan, . P., Hobbs, J. K.; Bullough, P. A. ‘Architecture and self-assembly of Clostridium sporogenes and Clostridium botulinum spore surfaces illustrate a general protective
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4. Pasquina-Lemonche, L., Burns, J., Turner, R. D., Kumar, S., Tank, R., Mullin, N., Wilson, J. S., Chakrabarti, B., Bullough, P. A., Foster, S. J., Hobbs, J. K. ‘The architecture of the Gram-positive bacterial cell wall’ Nature 582 (2020) 294-297.
1) The Stringent Response Inhibits 70S Ribosome Formation in Staphylococcus aureus by Impeding GTPase-Ribosome
Interactions.Bennison DJ, Nakamoto JA, Craggs TD, Milón P, Rafferty JB, Corrigan RM. mBio. 2021 Dec 21;12(6):e0267921. doi: 10.1128/mBio.02679-21. Epub 2021
2) Identification and structural analysis of the tripartite α-pore
forming toxin of Aeromonas hydrophila. Wilson JS,
Churchill-Angus AM, Davies SP, Sedelnikova SE, Tzokov SB, Rafferty JB, Bullough PA, Bisson C, Baker PJ. Nat Commun. 2019 Jul 1;10(1):2900. doi: 10.1038/s41467-019-10777-x.
3) Structural and functional characterisation of a stable,
broad-specificity multimeric sialidase from the oral pathogen Tannerella forsythia. Satur MJ, Urbanowicz PA, Spencer DIR, Rafferty J, Stafford GP. Biochem J. 2022 Sep
16;479(17):1785-1806. doi: 10.1042/BCJ20220244.
4) A New Mechanism for High-Affinity Uptake of
C4-Dicarboxylates in Bacteria Revealed by the Structure of Rhodopseudomonas palustris MatC (RPA3494), a Periplasmic Binding Protein of the Tripartite Tricarboxylate Transporter (TTT) Family. Rosa, L. T., Dix, S. R., Rafferty, J. B., & Kelly, D. J. (2019). J Molecular Biology, 431(2):351-367. doi:10.1016/j.jmb.2018.11.016.