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Investigating the pathogenesis of human papillomavirus (HPV) in anal cancers


   Faculty of Biological Sciences


About the Project

Infection with human papillomavirus (HPV) is associated with ~5% of all human cancers, in particular cervical cancer. Whilst less common, HPV is also associated with the vast majority (~93%) of anal cancers in the UK. Anal squamous cell carcinoma (ASCC) is a potentially fatal malignancy with a rising incidence. ASCC patients are faced with inadequate treatment protocols in which ~30% either do not respond or suffer relapse. As such identification of novel therapies is essential.

We currently lack a comprehensive understanding of how HPV causes anal cancer. To address this, we are collaborating with colleagues at St-James University Hospital to obtain biopsy sections of ASCC. You will use molecular biology techniques (e.g. RT-qPCR, western blot) to investigate the prevalence of HPV in these samples and to determine the viral type. You will then perform RNA sequencing analysis to reveal the global changes to host cell gene expression. Comparison of the gene expression changes will allow you to investigate the gene expression signature associated with HPV-driven ASCC and from there to study the host pathways and proteins required for transformation.

Applicants with a background in biological sciences, virology or biochemistry are particularly welcomed. Work in the Macdonald group uses a multidisciplinary strategy to understand the virus – host interactions that are crucial for virus-driven cancers. Students in our group have a 100% track record for successful completion of Ph.D studies within 4 years, and we are committed to the principles of equal opportunity and maintaining a positive laboratory culture. This project will be undertaken in collaboration with Dr Adel Samson a clinical oncologist at St-James University Hospital. Both supervisors are members of the Leeds Cancer Research Centre.

Eligibility: 

You should hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject. This project would suit someone with a strong background in tissue engineering, cancer biology or closely-related areas. Additional experience of conducting research in a multidisciplinary setting is highly desirable. Upon completion of the PhD, the successful candidate will be uniquely equipped for high-demand careers within academia or industry with desirable skills in bioengineering, regenerative medicine and cancer/cell biology.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

  • British Council IELTS - score of 6.0 overall, with no element less than 5.5
  • TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).
  • Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert

Funding Notes

Self-funded students: International or domestic self-funded or scholarship/fellowship PhD students are always welcome to apply. International students must have a good command of both written and spoken English. Most importantly, bench fees will be required if you are self-funded. Applications can be made throughout the year.

References

1. Morgan EL#, Patterson MR#, Ryder EL#, Lee S-Y#, Wasson CW, Harper KL#, Li Y#, Griffin S, Blair GE, Whitehouse A & Macdonald A. (2020). MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer. PLoS Pathogens 16(6): e1008624.
2. Morgan EL# & Macdonald A. (2019). JAK2 inhibition impairs proliferation and sensitises cervical cancer cells to Cisplatin-induced cell death. Cancers. 11(12): 1934.
3. Morgan EL# & Macdonald A. (2019). Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Rac1-NFB-IL-6 signalling axis. PLoS Pathogens. 15(6): e1007835.
4. Wetherill LF#, Wasson CW, Swinscoe G#, Kealy D#, Foster R, Griffin S & Macdonald A. (2018). Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5. Antiviral Research. 158: 113-121.
5. Morgan EL#, Wasson CW, Hanson L, Kealy D#, Pentland I, McGuire V, Scarpini C, Coleman N, Arthur JSC, Parish JL, Roberts S & Macdonald A. (2018). STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle. PLoS Pathogens. 14(4): e1006975.
6. Wasson CW, Morgan EL, Muller M, Ross RL, Hartley M, Roberts S & Macdonald A. (2017). Human papillomavirus type 18 E5 oncogene supports cell cycle progression and impairs epithelial differentiation by modulating growth factor receptor signalling during the virus life cycle. Oncotarget. 8(61): 103581-103600.

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