Host Advantage: Uncovering Protective Factors Against HPV‑Driven Cervical Cancers

About the Project

Who we are looking for

We are seeking a PhD student who is motivated by the process of scientific discovery and the opportunity to identify novel targets for anti-cancer therapies. A successful candidate will have good background knowledge of molecular and cell biology and will be comfortable with computational analyses. The project combines lab-based and computational research – experience of molecular biology and cell culture techniques would be advantageous, but full training will be given.

Together, we will uncover new insight into viral-host interactions at the gene/protein level, opening unexplored therapeutic possibilities.

Project outline

All viruses rely on interactions between viral proteins and host (e.g. human) proteins. This project will use a haploid cell screening system to identify host factors that are protective or permissive for human papillomavirus (HPV) proliferation. Almost all cervical cancer is caused by HPV infection, and we aim to identify factors that can be targeted for novel therapies. Haploid genetic screening using the eHAP cell line provides a powerful platform for identification of host factors whose disruption alters cellular fitness in the presence of a viral gene product.

Human papillomavirus, the principal cause of cervical cancers, encodes a set of early (E1–E7) and late (L1–L2) proteins that manipulate host pathways to promote viral replication, persistence, and cause cervical cancer. While individual HPV proteins have been extensively studied, the full spectrum of host genetic dependencies required for cells to tolerate or respond to each viral protein remains incompletely defined. In particular, the HPV proteins E6 and E7 are known to disrupt the function of the protective human proteins TP53 and RB1. To specifically investigate these effects of E6 and E7 on cancer initiation, reporter systems dependent on TP53 and RB1 will be used to allow FACS separation of affected cells.

By expressing each HPV protein individually in eHAP cells and inducing transposon mediated insertional mutagenesis, we can identify host genes whose loss confers resistance or sensitivity to the expression of specific viral proteins, and additionally any changes to TP53 and RB1 function. This approach will illuminate protein-specific host interactions, stress pathways, and potential therapeutic targets.

This project will generate the first systematic, protein-by-protein map of host genetic factors that modulate the cellular response to HPV gene expression. The findings will deepen our understanding of HPV biology, identify new therapeutic entry points, and provide a broadly applicable framework for studying other viral proteins using haploid genetic screening.

For this project you can expect a research environment in which supportive, experienced supervisors will encourage you to incrementally take ownership of the project as you develop your skills and expertise in this area. You will be working within a friendly group of molecular biologists and bioinformaticians with diverse backgrounds in various stages of their careers, from post-graduate students to professors.

The School of Pharmacy is a world top 5 school two years in a row, based on QS University rankings, and is joint 1st place in Research Environment with our colleagues from the Faculty Medicine and Health Sciences; we are joint 4th in the UK for research quality, with 96% of our research assessed as 'world-leading' or 'internationally excellent' (REF 2021). We work with over 30 leading companies across the healthcare sector, including Boots, Evonik, Mars Petcare UK, Promega, SureScreen Diagnostics, Syngenta, Unilever and Widex A/S.

The University actively supports equality, diversity and inclusion and encourages applications from all eligible sections of society. Candidates should be self-funded or have identified sources of funding to which they will apply. There may also be opportunities for similar projects investigating interactions in other viruses – please get in touch to discuss.

Join us at the forefront of world-changing research that’s both innovative and relevant, working on new therapeutic targets and treatments that will improve the lives of millions of people.

Enquiries should be sent to Dr Keith Spriggs (keith.spriggs@nottingham.ac.uk)