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Virus manipulation of host cell micro-RNAs to regulate gene expression


Project Description

micro-RNAs (miRNAs) are abundant endogenous RNAs and emerging evidence suggests they regulate gene expression by multiple processes. As such, miRNAs may play a central role in regulating a wide variety of biological processes and dysregulation of miRNAs expression may be implicated in human disease. We have exciting preliminary data suggesting that miRNA expression is manipulated by HPV to regulate downstream host signalling. This suggests that virus-mediated miRNA dysregulation plays a fundamental and essential role in regulating virus and host cell gene expression required for viral pathogenesis and tumourigenesis. The aim of this project is to determine how virus-mediated manipulation of host cell miRNAs regulate both virus and host cell gene expression during virus infection. Moreover, the project will identify novel host factors which regulate HPV replication and transformation, highlighting potential therapeutic approaches for the treatment of this important virus. The project will utilise a multidisiplinary approach involving cutting-edge techniques including mIR-seq profiling coupled with NGS analysis, bioinformatic analysis, confocal imaging and cell biology and use of physiological model cell culture systems.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2020:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference and research funding

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.

EU candidates require 3 years of UK residency to receive full studentship

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

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References

1. Nwogu, Boyne, Dobson, Poterlowicz, Blair, Macdonald, Mankouri & Whitehouse. Cellular sheddases are induced by Merkel Cell Polyomavirus Small Tumour Antigen to mediate cell dissociation and invasiveness. PLoS Pathogens. 6;14(9):e1007276. doi: 10.1371/journal.ppat.1007276.

2. Wetherill, Wasson, Swinscoe, Kealy, Foster, Griffin & Macdonald (2018). Alkyl-Imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5. Antiviral Research. pii: S0166-3542(18)30151-7. doi: 10.1016/j.antiviral.2018.08.005

3. Morgan*, Wasson*, Hanson, Kealy, Pentland, McGuire, Scarpini, Coleman, Arthur, Parish, Roberts & Macdonald (2018). STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle. PLoS Pathogens 9;14(4):e1006975. doi: 10.1371/journal.ppat.1006975.

4. Hurdiss, Frank, Macdonald* & Ranson* (2018). The structure of a pathogenic human polyomavirus and its interactions with distinct cellular receptors. Structure pii: S0969-2126(18)30123-0. doi: 10.1016/j.str.2018.03.019.

5. Panou, Prescott, Hurdiss, Swinscoe, Caller, Morgan, Carlisle, MÜller, Ranson, Crump & Macdonald (2018). Agnoprotein is an essential egress factor during BK polyomavirus infection. International Journal of Molecular Sciences. 19;19(3). pii: E902. doi: 10.3390/ijms19030902.

6. Stakaityte, Nwogu, Blair, Lippiat, Macdonald, Mankouri & Whitehouse (2018). Identification of cellular chloride channels that contribute to virus mediated cell motility. Journal of Biological Chemistry 293:4582-4590. doi:10.1074/jbc.RA117.001343.

7. Stakaitytė, Nwogu, Dobson, Knight, Wasson, Javier Salguero Bodes, Blackbourn, Blair, Mankouri, Macdonald & Whitehouse (2018). Merkel cell polyomavirus small T antigen enhances cell motility via Rho-GTPase-induced filopodia formation. Journal of Virology 2;92(2). pii: e00940-17. doi: 10.1128/JVI.00940-17.

8. Wasson, Morgan, Müller, Ross, Boxall, Hartley, Roberts & Macdonald (2017). Human papillomavirus type 18 E5 oncogene supports cell cycle progression and delays epithelial differentiation by modulating growth factor receptor signalling. Oncotarget. 6;8(61):103581-103600. doi: 10.18632/oncotarget.21658.

9. Abdul-Sada, MÜller, Mehta, Toth, Arthur, Whitehouse & Macdonald (2017). The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-kB by Merkel polyomavirus small T antigen. Oncotarget 11;8(15):25418-25432.

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

FTE Category A staff submitted: 60.90

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

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