PhD Studentship: Investigating the role of DNA2 in DNA replication, genome stability, and human disease.

Funding for: UK Students

Funding amount: Home (UK) tuition fees & stipend at standard UKRI rates.

A PhD studentship (3.5 years) is available from May 2025 under the supervision of Prof. Ulrich Rass and co-supervisor Dr Kok-lung (Chris) Chan, Genome Damage and Stability Centre, Centre of Excellence, School of Life Sciences.

Brief Description of the 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.

Informal enquiries about the project are welcome and can be made to:

Prof. Ulrich Rass u.w.rass@sussex.ac.uk

How to apply:

Please submit a formal application by clicking the 'Apply, above, attaching a CV, degree transcripts and certificates, & 2 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 Damage & Stability. Please select ‘funding obtained’ and state the supervisor’s name where required. Applicants with overseas fee status need to provide evidence showing how they will fund the difference between Home and International tuition fees (approx. £18k per year).

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