Investigating DNA damage tolerance and repair responses on mitotic chromosomes in human cells

We are seeking an enthusiastic and motivated PhD student to study the chromosome protection mechanism in human mitotic cells in an interdisciplinary project.

About The Project

DNA damage can occur in any phase of the cell cycle. Depending on the types of DNA lesion, chromatin environment and the cell cycle stage, cells employ different strategies to fix DNA lesions. Unrepaired and/or mis-repaired DNA molecules can accelerate genome instability, leading to genetic diseases and cancer development. Therefore, it is essential to repair DNA damage effectively and accurately to avoid daughter cells receiving incorrect genetic materials. Generally, Repairing DNA damage is relatively efficient on open, uncondensed chromatin. However, this poses a significant challenge to cells undergoing mitosis, as their DNA is tightly packed into highly condensed chromosomes. Thus, how mitotic cells can effectively repair DNA lesions in the context of compacted chromatin remains unknown.

The aims of this project are to understand the impact of DNA lesions on chromosome architecture and faithful chromosome segregation as well as the underlying mechanism of DNA damage responses in human mitotic cells. We also aim to apply the knowledge gained from this study to target cancer cells with high levels of mitotic DNA damage. The student will employ several cutting-edge technologies to study how human cells tolerate and repair DNA lesions during mitosis. The project will use genetically modified human cells as a model and combine advanced super-resolution imaging techniques and structural biology analysis. The student will learn a variety of research techniques including CRISPR genome editing, molecular biology, biochemistry, advanced fluorescent imaging, cytogenetics and cryoEM structural analysis.

The Team and Training

The student will be directly supervised from two senior research leaders at the Genome Centre. The successful PhD candidate will receive training from the two research teams with strong expertise in cell and chromosome biology, super-resolution imaging technology, cryo-electron microscopy and structural biology. We benefit from strong interactions with the Genome Centre, the Wolfson Centre of Biological Imaging, and Life Sciences. The student will also receive support to attend training workshops and scientific conferences provided by the host lab. We aim to nourish the next generation of scientists.

Informal enquiries about the project can be made to Dr. Chris Kok-Lung Chan at koklung.chan@sussex.ac.uk.

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 Damage and Stability. Please select ‘funding obtained’ and state the supervisor’s name where required.

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.