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Ross Chapman


Background to project 

Genomic instability (GI) is a hallmark of cancer that plays a central role in its initiation and development. GI can arise as a result of germline or somatic mutations that compromise a cell’s ability to accurately sense, signal or repair DNA damage. GI can also arise as a consequence of errors in chromosome segregation during mitosis, or when chromosome breakage events lead to chromosome rearrangements, and/or gains and losses to daughter cells following cell division. These catastrophic events are not only linked to tumour initiation, they also play a central role in cancers ability to evolve and acquire new aggressive traits, such as the ability to metastasize, or become resistant to anti-cancer therapies. However, in some specialised cell types, genome rearrangements must occur as programmed, highly orchestrated events, where they function to bring about genetic diversity.

Research in the Chapman laboratory aims to better understand the biological pathways that ensure DNA damage is accurately repaired, and their interplay with error-prone DNA end-joining mechanism that support programmed genome diversification as a physiological process. The laboratory has a long-standing interest in the BRCA1 tumour suppressor pathway, which coordinates the accurate repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) with an active suppression of mutagenic DNA end-joining mechanisms, such as non-homologous end joining (NHEJ)1–3. A complementary arm of our research studies the physiological purpose of the same mutagenic DSB repair pathways, such as in the adaptive immune system where NHEJ is essential4–6.

Project aims

The goal of this project is to investigate how tumour suppressor proteins including BRCA1 and ATM control the repair of DNA strand breaks, and better define their context and tissue specific function in proliferating and non-dividing cells. This will involve a combination of molecular cell biology, molecular genetics and biochemical approaches. The project will also involve genomics and cutting-edge genome editing technologies, such as targeted and screening applications of the CRISPR-Cas9 system. Where appropriate, mouse models will be used to define the physiological purpose of this biology, and the tissue and context-specific consequences of its inactivation or dysfunction in human disease and cancer.

Funded by Cancer Research UK. Funding is provided for fees at the home fee rate and a stipend of no less than £20K per year for four years.



Interdisciplinary by design, DPhil projects will utilise a broad range of cutting-edge molecular and genetic technologies, and will foster interactions with multiple labs in the WIMM. Experimental approaches in the lab include advanced molecular biology, quantitative proteomics, quantitative and super-resolution imaging, CRISPR-Cas9 genome editing, structural biology and transgenic mouse models. The laboratory also utilises genome-wide screening approaches, and is developing methods to analyse the repair of endogenous DNA breaks on a genome scale. Training opportunities at the WIMM also exist to develop expertise in basic and advanced bioinformatics.

Students will be enrolled on the MRC WIMM DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.




1. Becker, J. R., Clifford, G., Bonnet, C., Groth, A., Wilson, M. D. & Chapman, J. R. BARD1 reads H2A lysine 15 ubiquitination to direct homologous recombination. Nature 596, 433–437 (2021).

2. Nakamura, K., Saredi, G., Becker, J. R., Foster, B. M., Nguyen, N. V., Beyer, T. E., Cesa, L. C., Faull, P. A., Lukauskas, S., Frimurer, T., Chapman, J. R., Bartke, T. & Groth, A. H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nat Cell Biol 21, 311–318 (2019).

3. Chapman, J. R., Sossick, A. J., Boulton, S. J. & Jackson, S. P. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair. J Cell Sci 125, 3529–3534 (2012).

4. Ghezraoui, H., Oliveira, C., Becker, J. R., Bilham, K., Moralli, D., Anzilotti, C., Fischer, R., Deobagkar-Lele, M., Sanchiz-Calvo, M., Fueyo-Marcos, E., Bonham, S., Kessler, B. M., Rottenberg, S., Cornall, R. J., Green, C. M. & Chapman, J. R. 53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ. Nature 560, 122–127 (2018).

5. Becker, J. R., Cuella-Martin, R., Barazas, M., Liu, R., Oliveira, C., Oliver, A. W., Bilham, K., Holt, A. B., Blackford, A. N., Heierhorst, J., Jonkers, J., Rottenberg, S. & Chapman, J. R. The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity. Nat Commun 9, 5406 (2018).

6. Xu, G., Chapman, J. R., Brandsma, I., Yuan, J., Mistrik, M., Bouwman, P., Bartkova, J., Gogola, E., Warmerdam, D., Barazas, M., Jaspers, J. E., Watanabe, K., Pieterse, M., Kersbergen, A., Sol, W., Celie, P. H. N., Schouten, P. C., Broek, B. van den, Salman, A., Nieuwland, M., Rink, I. de, Ronde, J. de, Jalink, K., Boulton, S. J., Chen, J., Gent, D. C. van, Bartek, J., Jonkers, J., Borst, P. & Rottenberg, S. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 521, 541–544 (2015).