Life Sciences PhD Genome Stability - Investigating the role of DNA2 in DNA replication, genome stability, and human disease. (2025)

What you get

This School-funded position covers Home (UK) tuition fees and a stipend (standard UKRI rate) for 3.5 years. Applicants with overseas fee status must provide evidence showing how they will fund the difference between Home and International fees (approx. £20k per year).

Type of award

Postgraduate Research

PhD project

DNA2 was first described three decades ago and has since been the subject of ever-increasing interest due to its essential requirement for cell proliferation and links to human disease. Low expression of DNA2 results in primordial dwarfism disorders such as Seckel and Rothmund-Thomson syndrome; DNA2 over-expression on the other hand, is frequent in cancer and DNA2 is now recognized as a potential target for cancer therapy. On the molecular level, DNA2 is implicated in Okazaki fragment processing, DNA double-strand break repair, and the recovery of stalled DNA replication forks (PMID: 33924313). Our previous work has indicated that replication fork recovery by DNA2 is critical for faithful chromosome replication (PMID 27779184 & 32544229), and we suggest that DNA2 dysfunction results in toxic DNA intermediates by way of unscheduled recombination at replication forks left unresolved by DNA2 (PMID: 32909097). We have now engineered human cell lines allowing controlled degradation of DNA2 which has opened up a number of hitherto intractable fundamental and translational research questions.

During this Centre of Excellence studentship, you will investigate how DNA replication, DNA replication fork recovery, and homologous recombination cooperate to make a perfect copy of the human genome that can be passed on to healthy daughter cells. We will explore which regions of the genome depend on DNA2 for replication, why they are susceptible to toxic recombination, how this leads to chromosome instability, and why DNA2 over-expression provides a selection advantage to cancer cells. The results will shed new light on some of the most central processes of life, elucidate the molecular mechanisms underpinning primordial dwarfism disorders, and inform the development of emerging small-molecule DNA2 inhibitors as anti-cancer therapeutics.  

This is an outstanding opportunity to join a momentous line of research. As studentship holder, you will work alongside a highly experienced postdoctoral research associate (PRDA) and receive training in molecular biology, CRISPR-mediated genome engineering of human cell lines, and cytogenetic analyses. The project co-supervisor Chris Chan is a leading expert in cutting-edge fluorescent imaging, and you will have access to instruction in state-of-the-art microscopy within our Wolfson Centre of Biological Imaging. We provide an inclusive lab environment, and the Genome Damage and Stability Centre is home to a highly collaborative community of scientists. There will be opportunities to attend training workshops and scientific conferences.

Eligibility

Candidates should have/expect a minimum BSc 2:1. MSc degree/experience in a laboratory setting advantageous. Qualification should be in Biochemistry, Biomedical Sciences, or a related area. You may be considered if you have other professional qualifications or experience of equivalent standing.

Candidates for whom English is not their first language must include a document listed here:  English language requirements

Applications are particularly welcomed from candidates with protected characteristics – e.g., from Black and other ethnic minorities who are under-represented in postgraduate research at our institution.

Deadline

How to apply

Please submit a formal application using the online admissions portal attaching a CV, degree transcripts and certificates, and two academic referees.

A research proposal is not required. Instead, please upload a personal statement describing your subject areas of interest, skills and previous experience, motivation for Doctoral Research, future goals, and why you are applying to this project.

On the application system select Programme of Study – PhD Genome Stability. Please select ‘funding obtained’ and state the supervisor’s name where required.

Contact us

Informal enquiries about the project are welcome and can be made to: Prof. Ulrich Rass: u.w.rass@sussex.ac.uk

For queries about the application process, please see the online application guide or contact Emma Chorley: lifesci-rec@sussex.ac.uk

Futher information:

https://profiles.sussex.ac.uk/p466497-ulrich-rass/about

https://profiles.sussex.ac.uk/p350627-kok-lung-chan