PhD Studentship: Interactions between the Human Papillomavirus (HPV) oncogenes and the ubiquitin system

Ph.D. studentship (3.5 years) is available from September 2023 under the supervision of Dr Ethan Morgan and Professor Michelle West, Department of Biochemistry, School of Life Sciences.

Deadline: 15/01/2023

Title: Interactions between the Human Papillomavirus (HPV) oncogenes and the ubiquitin system

About the Project 

Human papillomaviruses (HPV) infect the oral and ano-genital epithelia. Persistent HPV infection is associated with the development of several malignancies, including cervical cancer and head and neck squamous cell carcinoma (HNSCC). The primary viral oncogenes, E6 and E7, manipulate many cellular processes in order to promote cell proliferation and survival. Despite a good understanding of how HPV E6 and E7 promote tumour development, further research is required to identify novel therapeutics for HPV and HPV-associated cancers. 

Protein ubiquitination plays a broad, critical role in the regulation of most cellular processes and many oncogenes and tumour suppressors are regulated by ubiquitin-mediated degradation. The most well-studied oncogenic function of HPV E6 and E7 is the proteasomal degradation of the tumour suppressors p53 and pRb, respectively. Therefore, manipulation of protein ubiquitination is a common mechanism of HPV-induced oncogenesis. Furthermore, the protein ubiquitination pathway is becoming an attractive therapeutic target in drug development for novel cancer treatments.

Objectives

This PhD studentship will use a range of biological and biochemical techniques to investigate how the HPV oncogenes interact with the ubiquitin machinery using multiple cervical cancer and HNSCC cell models. The project will use complementary screening methods to identify interactions between the HPV E6 and E7 and components of the ubiquitin machinery. The function of identified host interactors will be analysed for their role in HPV-associated malignancy using a range of phenotypic assays to assess proliferation, survival, migration/invasion, response to radio/chemotherapy, etc.

This project combines phenotypic cell culture assays with laboratory techniques such as real-time PCR, confocal microscopy and flow cytometry. The long-term goal of the project is to identify novel mechanisms by which the HPV E6 and E7 promote tumour development and has the potential to uncover novel targets to treat HPV-associated cancers.

How to apply:

Please submit a formal application using our online system at www.sussex.ac.uk/study/phd/apply attaching a CV, degree transcripts and certificates, statement of interest and two academic references.

On the application system select: Programme of Study – PhD Biochemistry. Please ensure you state the project title under funding and include the proposed supervisor’s name where required.

This School-funded position covers Home tuition fees and a stipend at standard UKRI rates. Applicants with overseas fee status will need to fund the difference between Home and International tuition fees (approx. £18k per year).

Ideal candidates will have a strong background in cancer virology/biology or cell biology. Eligible applicants will hold a 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.

For enquiries about the application process, contact Emma Chorley: lifesci-rec@sussex.ac.uk

For enquiries about the project, contact supervisor: ethanlmorgan@msn.com

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