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Molecular mechanisms of host cell transcription factor hijack by the cancer-associated Epstein-Barr virus


Project Description

Background: Epstein-Barr virus (EBV) drives the development of numerous human cancers, including Burkitt, Hodgkin and post-transplant lymphoma and nasopharyngeal and gastric carcinoma. The virus infects B cells and drives their deregulated growth and immortalisation. This is a key cancer-promoting property of the virus. Four EBV transcription factors (EBNA2, 3A, 3B and 3C) play a critical role in B cell immortalisation by altering the transcription of hundreds of B cell genes involved in growth and survival. These viral transcription factors however do not bind to DNA directly. They interact with host cell transcription factors to gain access to host gene regulatory elements (promoters and enhancers) to alter gene expression.

Project: The overall aim of this project is to use biochemical, genomic, biophysical and structural biology approaches to study how interactions between EBV transcription factors and host cell transcriptional regulators promote B cell immortalisation. The project is a collaboration between the groups of Professor Michelle West and Dr Chrisostomos Prodromou.

Impact: This work will provide key information on how EBV drives cancer development, how transcription factor complexes function in normal and disease contexts and may highlight new targets and interaction surfaces for the development of new therapies for EBV-associated diseases.

Applicant: The project would suit an enthusiastic and committed recent life-sciences graduate interested in joining a friendly and hard-working team of scientists working on gene regulation, transcription factor complexes and their role in blood cancer development. Ideal candidates will have recently received an MSc and/or a First or high 2:1 BSc in a relevant subject. Candidates for whom English is not their first language will require an IELTS score of 6.5 overall, with not less than 6.0 in any section.

Please submit a formal application using our online application system at http://www.sussex.ac.uk/study/phd/apply, including a CV, degree transcripts and certificates, statement of interest and names of two academic referees.
On the application system use Programme of Study – PhD Biochemistry. Please make sure you include the project title and Supervisor’s name with your statement of interest on the application form.

Funding Notes

This School funded position, which covers fees and a stipend at standard RCUK rates, is open to Home / EU applicant only.

References

1. Wood CD, Carvell T, Gunnell A, Ojeniyi OO, Osborne C, West MJ (2018). Enhancer control of miR-155 expression in Epstein-Barr virus infected B cells. Journal of Virology. Jul 18. pii: JVI.00716-18. doi: 10.1128/JVI.00716-18.
2. West, M. J. (2017). Chromatin reorganisation in Epstein Barr virus-infected cells and its role in cancer development. Current Opinion in Virology 26C pp. 149-155. doi: 10.1016/j.coviro.2017.08.004.
3. Wood CD, Veenstra H, Khasnis S, Gunnell A, Webb HM, Shannon-Lowe C, Andrews S, Osborne CS, West MJ (2016). MYC activation and BCL2L11silencing by a tumour virus through the large-scale reconfiguration of enhancer-promoter hubs. Elife. Aug 4;5. pii: e18270. doi: 10.7554/eLife.18270.
4. Gunnell, A., Webb, H. M., Wood, C. D., McClellan, M. J, Wichaidit, B., Kempkes, B., Jenner, R. G., Osborne, C., Farrell P. J., West. M. J. (2016). RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth. Nucleic Acids Research. 44, 4636-50. doi: 10.1093/nar/gkw085.

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

FTE Category A staff submitted: 47.61

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