Single-molecule visualisation of the eukaryotic replication machinery

A 2025 Crick PhD project with Hasan Yardimci.

Accurate genome duplication is essential for cell division and genetic integrity in all living organisms. Errors in DNA replication can lead to genome instability, which is a hallmark of cancer and other diseases. To understand the molecular mechanisms that ensure faithful DNA replication, we use live single-molecule fluorescence microscopy alongside ensemble biochemical methods.

Our lab employs two key in vitro systems: Xenopus laevis egg extracts, which provide a powerful system for studying DNA replication in a near-native environment, and a fully reconstituted system with purified proteins, allowing us to dissect replication mechanisms with precise molecular control.

This project focuses on understanding how replisome factors coordinate to duplicate chromatin and how they respond to replication barriers. Using live imaging, we aim to visualise how the replication machinery interacts with chromatin in real time. We will uncover the molecular details of how replisome components work together to overcome obstacles during genome duplication.

Candidate background

This project is well-suited for candidates with a background in biochemistry, biophysics, or molecular biology who are interested in applying cutting-edge imaging and biochemical methods to study fundamental aspects of DNA replication.