Using a novel anal epithelial cell culture model to better understand the human papillomavirus lifecycle and anal cancer progression

About the Project

The School of Molecular and Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2025/26.

We especially welcome applications that connect to the School's core research areas, which are understanding life in molecular detail, with particular relevance to infectious diseases and cancers.

The human papillomavirus (HPV) is responsible for 5% of human cancers including cervical, other anogenital and an increasing number of oral cancers. HPV is prevalent in low and middle income countries, where access to the HPV vaccine is limited. Despite its importance, there are no good antiviral drugs for HPV-associated cancers. Therefore, understanding how HPV causes cancer is crucial to aid in the identification of new targets for therapy.

The Macdonald lab is recognised as an international leader in the study of HPV–host interactions and in understanding which signalling pathways contribute to disease (selected recent high impact publications from the lab PMID:38987584; PMID: 38789663; PMID: 33427604).

For this project we will use a newly developed primary cell culture model of HPV infection of the anal epithelium. Such powerful models have transformed our understanding of the cervical and oral epithelium, revealing differences in host signalling and transcriptional programmes in response to infection at these distinct anatomical sites, and providing clues to the mechanisms driving differences in the pathogenesis of HPV in different tissues. In contrast, we know next to nothing of the biology of HPV infection of the anal epithelium. This is detrimental in the face of increasing incidence of HPV-positive anal cancers, disproportionately impacting individuals with low incomes and racial and ethnic minority groups.

Our objectives are to determine how HPV changes the proliferation and differentiation of the anal epithelial in monolayer and 3D culture. We will combine RNA-sequencing, proteomic and computational analysis to understand transcriptional re-programming in response to HPV infection and characterise the functions of de-regulated target genes in epithelial biology, the HPV lifecycle and using a large cohort of clinical trial patient samples, finally assess their role in anal cancer. Ultimately, we will provide new biological knowledge and insights into this crucial pathogen.

The Macdonald group is based in newly refurbished lab space, is highly supportive, well-funded and is situated in close proximity to core research infrastructure. Our people centric approach ensures that all graduate students in the group are appropriately mentored, have the opportunity to grow as scientists, to present their data to colleagues, to publish appropriate research and to be guided to the next stage of their career. We are collaborative and work with scientists, clinicians and industrialists in Leeds and beyond to undertake impactful research.

Eligibility

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline.

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
• Internet based TOEFL - overall score of 80 (with not less than 17 in listening, 18 in reading, 20 in speaking and 19 in writing). Tests must be taken at a test centre.

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

For information about the application process please contact the Faculty Admissions Team:

e: fbsgrad@leeds.ac.uk

Funding Notes

This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.