PhD project

Supervisor: Anjali Hinch

The chromosomes we inherit from our parents are not exact copies but mosaics of their chromosomes. These mosaics are created during the formation of eggs and sperm when cells cut chromosomes up and re-attach them, sometimes in new combinations (recombination). We have found that our cells make an unexpectedly large number of errors in this process leading to changes in DNA (mutations). Our DPhil projects aim to answer fundamental questions on the nature of human de novo mutation and recombination, the mechanisms that generate them and their consequences on our health. 

We take a data-driven approach to address these questions. Processes underlying de novo mutation and meiotic recombination are complex and dynamic, involving the interplay of numerous proteins. Our approach involves utilising large-scale genetic datasets such as the UK Biobank as well as performing a range of experimental assays including CRISPR-mediated genome-editing. We then use machine learning and other statistical techniques to characterise their interactions. 

Please see the project webpage for more details.

Publications:

• Hinch, R., Donnelly, P., Hinch, A.G. Meiotic DNA breaks drive multifaceted mutagenesis in the human gemline. Science (In press).
• Hinch, A.G., Becker, P. W., Li, T., Moralli, D., Zhang, G., et al. The configuration of RPA, RAD51 and DMC1 binding in meiosis reveals the nature of critical recombination intermediates. Molecular Cell.  (2020).
• Anjali G Hinch, Gang Zhang, Philipp W Becker, Daniela Moralli, Robert Hinch, et al. Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm. Science. Vol. 363, Issue 6433 (2019).
• Davies B, Hatton E, Altemose N, Hussin JG, Pratto F, Zhang G, Hinch AG, et al. Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. Nature. 530, 171-176 (2016).
• Anjali G Hinch, Arti Tandon, Nick Patterson, Yunli Song, Nadin Rohland, et al. The landscape of recombination in African Americans. Nature. 2011; 476: 170-175.