Project No. – 2025

Primary Supervisor

Prof Neil Kad – University of Kent

Co-Supervisor(s)

Prof Laurence Pearl – University of Sussex

Dr Antony Oliver – University of Sussex

Summary

Genome maintenance is crucial to the survival of all organisms.

Defects in this process can lead to the formations of cancerous tumours or to premature ageing. Therefore, all organisms expend large amounts of energy to interrogate, maintain and repair their genomes. This is primarily achieved by proteins of specialised DNA repair pathways that search the genome for damage and signal the need for repair. To achieve this efficiently, multiple proteins then need to coalesce around the sites of damage forming the complex machinery required for repair. This project is aimed at understanding how these proteins work together to form such complexes, and in turn how the resultant complexes function to repair DNA.

In this project you will be studying the molecular mechanisms of DNA repair using a plethora of state-of-the-art techniques. In Sussex, you will learn protein biochemistry and investigate the structures of these complexes using cryo-electron microscopy. In Kent, you will use single molecule imaging to directly visualise the formation and function of these DNA repair machines.

We aim to understand the molecular basis of a number of repair systems; but will focus on understanding how different ‘clamps’ are loaded onto DNA and how they stimulate the subsequent assembly of multimeric complexes.

Our ultimate goal is to view these protein complexes assembling and performing their functions in real-time. This data coupled with high resolution structural information, will answer some of the most challenging questions in the field of eukaryotic DNA repair.