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MRC DiMeN Doctoral Training Partnership: Why do multiple pathogenic viruses including HIV, Influenza, Ebola, Herpesviruses and Adenovirus target the cellular transcription machinery?

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  • Full or part time
    Prof S A Wilson
    Prof A Whitehouse
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Viruses frequently hijack cellular processes as part of their life cycle. A recent proteomics screen revealed a core of mammalian proteins which are targeted by multiple viruses, defining four critical cellular nodes in viral infections (Nature 487:486-490). One of these proteins, hnRNPU, was further shown to inhibit the influenza polymerase activity and replication of vesicular stomatitis virus. Additionally, hnRNPU targets viral proteins from Ebola virus, Herpes Simplex virus and Kaposi’s Sarcoma-associated Herpesvirus. Independently overexpression of a fragment of HNRNPU was shown to suppress HIV1 replication (Mol Cell 23:597-605). The cellular function of HNRNPU has remained enigmatic, though recent work suggests it plays a role in chromatin organisation ( Cell 169:1214-1227). We have now identified a critical role for hnRNPU in transcription in human cells. In this project you will investigate the interplay between viruses and HNRNPU in the context of cellular transcription and chromatin organisation. This work may lead to new therapeutic strategies in the future for treatment of viral infections. The two laboratories involved use a wide range of cutting edge techniques and training would be provided. These include CRISPR engineering of mammalian cell lines, genome wide approaches to gene expression analysis such as CHIP-seq, mNETseq and iCLIPseq combined with bioinformatics analysis of large scale datasets. We also make full use of proteomic and microscopy techniques to understand the fundamental processes of gene expression in the context of viral infections.

The project will be primarily based in Sheffield (Wilson lab) - http://genome.sheffield.ac.uk/people/professor-stuart-wilson/ but will work closely with the Whitehouse laboratory in Leeds http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=AWhi
where training in virology will be provided. The two laboratories have a long standing track record of successful collaboration.

Informal enquiries are welcome to either [Email Address Removed] or [Email Address Removed]

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: https://goo.gl/8YfJf8
Good luck.

References

Recent papers from the two labs include:
Viphakone, N., Cumberbatch, M.G., Livingstone, M., Heath, P.R., Dickman, M.J., Catto, J.W. and Wilson, S.A. (2015) Luzp4 defines a new mRNA export pathway in cancer cells. Nuc Acids Res. 43:2353-66

Viphakone, N., Hautbergue, G.M., Walsh, M., Chang, C.T., Holland, A., Falco, E.G., Reed, R. and Wilson, S.A. (2012) TREX exposes the RNA binding domain of Nxf1 to enable mRNA export. Nature Communications, 3:1006

Schumann S, Jackson BR, Yule I, Whitehead SK, Revill C, Foster R, Whitehouse A . Targeting the ATP-dependent formation of herpesvirus ribonucleoprotein particle assembly as an antiviral approach Nature Microbiology 2 -, 2017

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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