Human tissue models of bladder cancer initiation to guide new prevention strategies

About the Project

Lead supervisor:Dr Simon Baker

Co-supervisors:Prof Will Brackenbury

The student will be registered with the Department of Biology

Background

BK polyomavirus is a ubiquitous infection that nearly everyone acquires during childhood. Once we have been infected with BK virus, it establishes a persistent infection of the kidney, where it is largely kept under control by the immune system. However, during periods of immune limitation (or under immunosuppression) BK virus can reactivate and infectious virions can then be found in the urine. We have been collecting evidence suggesting BK virus may be an important risk factor for bladder cancer development. The host laboratory specialises in human tissue models of the epithelium that lines the urinary tract including the bladder, which is known as “urothelium”. Infection of urothelial tissue models with BK virus leads to the induction of antiviral “APOBEC3” cytosine deaminases. APOBEC3 enzymes evolved to damage viral genomes but can cause collateral DNA damage in host cells and are known to be the major source of point mutations in bladder cancer genomes. The question

Smoking is currently the main established risk factor for bladder cancer and understanding how smoke carcinogens might interact with infection to exacerbate carcinogenesis is a key question. The mechanism could involve exacerbating APOBEC mutagenesis because there is little evidence for direct genomic damage by smoke carcinogens in bladder tumour genomes. A key difference between normal tissues which can harbour APOBEC point mutations (https://www.science.org/doi/10.1126/science.aba8347) and cancers is the presence of larger scale structural damage to the genome.

This project will seek to model bladder cancer initiation in human tissue models with a focus on creating the conditions required to drive larger structural variants observed in bladder cancer genomes.

Training

This project will give the student training in primary human tissue models, toxicology, virology and cutting-edge genomics. Specific laboratory techniques you will learn will include tissue culture and development of tissue models of infection (https://www.nature.com/articles/s41388-022-02235-8), RNA/DNA isolation, RNA-sequencing, high-fidelity duplex Nanorate DNA sequencing (https://www.nature.com/articles/s41586-021-03477-4).

The primary supervisor can be found on LinkedIn or Bluesky @drsimonbaker.bsky.social and you can hear more about the research area in this talk on Youtube (https://www.youtube.com/watch?v=Kc65eA2wglA&t=1010s).

Our work on virus-induced mutational signatures can be found in Science Advances (https://www.science.org/doi/10.1126/sciadv.aea6124) and our initial work on urothelial BK virus infections and APOBECs is in Oncogene (https://www.nature.com/articles/s41388-022-02235-8).

Our latest work on virus-induced mutational signatures is currently in peer review but you can find more information on urothelial BK virus infections and APOBECs in our Oncogene paper (https://www.nature.com/articles/s41388-022-02235-8).

The University of York is committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

The Department of Biology holds an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.

Entry Requirements:

Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with any biological, chemical, and/or physical science backgrounds.

Programme: PhD in Biomedical Science (3 year)

Start Date: 21 September 2026

Funding Notes

Students need to have adequate funds to cover 3 years of tuition fees and living expenses