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Understanding fundamental aspects of viral capsid maturation in enteroviruses


   Faculty of Biological Sciences

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  Prof N J Stonehouse, Prof D.J. Rowlands, Dr Natalie Kingston  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Enteroviruses are responsible for a wide variety of diseases ranging from paralysis and death (e.g. poliovirus) to the common cold. Many new enteroviruses have been identified in recent decades and are of global concern as emerging pathogens. One notable example would be EVD68.

The project is aligned with our NIH-funded research to investigate the molecular mechanism of enterovirus (EV) capsid maturation. Proteolytic cleavage of the capsid VP0 protein is a key event in the virus assembly process and renders the virus particle infectious and primed for the conformational changes which accompany cell entry. It is therefore of key importance for a more complete understanding of the virus assembly process and will also provide insights into potential targets for the development of antiviral therapeutic drugs.

The project will combine in silico, evolutionary, and structural approaches to determine the functional role of critical amino acid residues and capsid reorganisation associated with VP0 cleavage. The successful candidate will help to establish new methods for the characterisation of viruses required to understand capsid maturation. This will include the generation of a comprehensive EV sequence library and the identification of sites and conformations showing pan-EV conservation. These findings will inform the generation of mutant EVs which will be investigated biochemically, structurally and evolutionarily to better understand the molecular basis of viral maturation. This project will culminate in the selection and characterisation of compounds (small molecules) which target the enterovirus maturation pathway.

Eligibility

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. A Masters degree is desirable but not essential.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

How to apply

To apply for this scholarship opportunity applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable)

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert
  • For source of funding please state you are applying for an advertised Faculty Scholarship

As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Within the Faculty of Biological Sciences we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+; and people with disabilities. Applicants will always be selected based on merit and ability. 

For more information about this scholarship and how to apply please contact [Email Address Removed]


Funding Notes

This scholarship will attract an annual tax-free stipend of £16,062 for up to 4 years, subject to satisfactory academic progress. The award will also cover the academic fees at the UK fee rate. Due to limited funding we can only consider applicants for this position who are eligible to pay academic fees at the UK fee rate.

References

Kingston J., Grehan K., Snowden J.S., Shegdar M., Fox H., Macadam A., Rowlands D.J., Stonehouse N.J. (2022) Development of an ELISA for the detection of the native conformation of enterovirus A71. MSphere https://pubmed.ncbi.nlm.nih.gov/35642505/
Kingston J., Shegdar M., Snowden J.S., Fox H., Groppelli E., Macadam A., Rowlands D.J., Stonehouse N.J. Thermal stabilisation of enterovirus A71 and production of antigenically stabilised empty capsids. J. General Virology in press
Kelly J., De Colibus L., Elliot L., Fry E.E., Stuart D.I., Rowlands D.J. and Stonehouse N.J. (2015) Potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or Coxsackievirus A16. Antiviral Res. 124, 77-82.
De Colibus L., Wang X., Spyrou J.A.B., Kelly J., Ren J., Grimes J., Puerstinger G., Stonehouse N., Walter T.S., Hu Z., Wang J., Li X., Peng W., Rowlands D.J., Fry E.E., Rao Z and Stuart D.I. (2014) More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules. Nature Structural Molecular Biology, 21, 282-288.

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