BACKGROUND
Research in the Hughes lab at the University of St Andrews focuses on antiviral responses and the regulation of innate immunity. As part of our first-line defence against viral infection, our cells produce cytokines, such as interferons (IFN). IFNs bind to receptors expressed on all nucleated cells resulting in activation of JAK/STAT signalling and the expression of hundreds of IFN-stimulated genes (ISGs). The main role of this large response is to create an unfavourable environment for virus replication and to limit transmission. However, it must be tightly regulated to avoid an over-exuberant immune response that would cause devastating autoinflammatory disease and tissue damage. Importantly, some ISGs play major roles in regulating the response, ensuring it is strong enough to combat the infection but not so strong that it causes disease. A very important protein that plays this role is the ubiquitin-like protein ISG15; in fact, patients unable to produce ISG15 suffer terribly from autoinflammatory diseases as a result of a dysregulated IFN response.
The mechanistic details of how ISG15 regulates type I IFN signalling are only just emerging, but other roles for this fascinating protein are still enigmatic. For instance, there is still no unified understanding of the cellular role for ISGylation (the covalent attachment of ISG15 to proteins) during the antiviral response. It is emerging that ISGylation may be important for autophagy during host defence response.
Autophagy is a fundamental process that degrades cellular components to promote homeostasis. Its role in regulating the antiviral response is well established: it regulates the magnitude of the response and can target specific pathogens, including viruses for destruction. As is common during the evolutionary arms race between pathogen and host, many viruses have developed ways of counteracting the antiviral activity of autophagy or even taking advantage of it and turning it into a proviral process.
Experiments in the Hughes Lab have linked ISG15 to autophagy which leads to several intriguing questions this PhD project aims to address:
· How does ISG15 influence autophagy during an antiviral response?
· How do the structural features of ISG15 regulate autophagy?
· What pathway-specific interactions does ISG15 regulate during an antiviral response?
This highly focussed project will provide training in molecular virology, CRISPR/Cas9 genome editing, cutting-edge proteomics and state-of-the-art imaging.
You will be part of a productive and supportive research team that encourages personal development by providing training opportunities beyond the lab.
Please direct informal enquiries to Dr David Hughes ([Email Address Removed])
Lab website: https://hugheslab.weebly.com/
HOW TO APPLY
Details of the competition and how to apply are given here: https://www.st-andrews.ac.uk/study-abroad/global-research/csc/
Applicants must submit an application for entry onto the School's PhD programme. Please do this via the Online Application Portal by the 9th January 2023. Once submitted, applicants must also submit a separate application for the scholarship by Thursday 12th January 2023.
We require the following documents; CV, personal statement, 2 references, academic qualifications, English language qualification.
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