Structures and mechanisms of genome replication

Accurate and timely genome replication is essential for all forms of life. This process is orchestrated by a multi-protein assembly termed the replisome, which drives both the fundamental steps of DNA replication, and co-ordinates this process with epigenetic inheritance, the establishment of sister chromatid cohesion, and multiple forms of DNA repair. Recent advances in biochemical reconstitution and DNA sequencing, as well as structural biology using both cryo-EM and AI-based approaches, have driven an explosion of knowledge in the field, making this a very exciting time for DNA replication research.

Our laboratory uses biochemical reconstitution with purified yeast and human proteins, molecular genetics and structural biology to examine key aspects of genome replication. Current projects include but are not limited to understanding a) the process of DNA replication termination in molecular detail b) the function of accessory DNA helicases in genome replication and c) the mechanisms involved in assembling the catalytic core of the CMG replicative helicase.

We are looking for an enthusiastic student to join our laboratory and undertake an ambitious project aimed at developing cryo-EM approaches to tackle some of the above questions. The successful candidate would acquire expertise in protein purification and complex biochemical reconstitutions and, in collaboration with the cryo-EM facility at the Max Delbruck Centre in Berlin, gain world class training in cryo-EM. Overall, this is an opportunity to work on exciting, fundamental aspects of genome replication in a focussed and nurturing environment.

For informal enquiries about this project, please contact Tom Deegan (tdeegan@ed.ac.uk).