Postgrad LIVE! Study Fairs

Birmingham | Edinburgh | Liverpool | Sheffield | Southampton | Bristol

London School of Hygiene & Tropical Medicine Featured PhD Programmes
Bournemouth University Featured PhD Programmes
Imperial College London Featured PhD Programmes
Imperial College London Featured PhD Programmes
University College London Featured PhD Programmes

Exploring the molecular mechanisms of CREB activation in the human papillomavirus (HPV) infected epithelium

Project Description

Human papillomaviruses re-wire an infected keratinocytes to drive virus replication and persistence. In so doing, they cause a number of devastating cancers in both sexes. To generate novel therapeutics it is essential to understand the complexities of the virus lifecycle. We have established a number of primary cell culture models that allow study of the entire HPV life cycle, and coupled with clinical data we use these resources to understand the interactions between HPV and the host. In this project we will focus on the CREB transcription factor and identify its contribution to HPV replication and pathogenesis. The project will combine virology and cell biology with state of the art cell culture models to provide novel insights into fundamental biology. It will be based in the Macdonald and Whitehouse laboratories, which are internationally recognised for their work on DNA tumour viruses.

More information on research in the Macdonald laboratory can be found at:

Objectives of the project
We will combine primary cell culture models with genetic and cellular approaches to study the role of CREB in virus replication and transformation. In particular, we will focus on three key areas:
1) Impact of HPV infection or oncoprotein expression on cellular regulators of CREB including upstream protein kinases
2) Contribution of CREB associated pathways to HPV replication and transformation using small molecule inhibitors and expression of dominant active/negative mutants
3) Identify which virus coded proteins are responsible for subverting CREB function using lentiviral transduction of individual genes, genetic manipulation of the full-length virus and mutagenesis of the gene product.

This study will provide unprecedented information on a critical host factor shown to be deregulated by an oncogenic virus.

Training for the PhD student
The student would be based in a large, productive group that uses multidisciplinary approaches to understand virus-host interactions that are critical for HPV infection and transformation. They would be exposed to a range of cutting edge techniques including primary cell culture models, genetic manipulation, pharmacological inhibition of key host pathways, RNASeq and chromatin immunoprecipitation (ChIP). The Macdonald and Whitehouse laboratories are well funded and routinely publish in high impact journals in the field of virus-host interactions (see references). All PhD students supervised by Macdonald have graduated with their PhD within the stipulated time, have published primary research, have presented their research at international conferences and have secured graduate employment soon after leaving the group.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

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 in order to receive full studentship

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

View Website


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)

Click here to see the results for all UK universities

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully

FindAPhD. Copyright 2005-2018
All rights reserved.