An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

We are based in the Department of Zoology at the University of Cambridge where we study the processes that occur at replications forks and in replication factories in mammalian cells. Cells have to coordinate a large number of activities at each replication fork, and this seems to involve the key replication protein PCNA that acts as a sliding clamp to recruit enzymes and regulators of DNA replication to the right place at the right time. I am in the process of moving the group to the Wellcome Trust Centre for Human Genetics in Oxford. There we will continue to study genetic and epigenetic stability during DNA replication, but we will be looking also at the origins of chromosomal alterations: copy number variations and translocations, and the relationship between these, replication timing and the three dimensional organisation of the nucleus.

Projects in the lab include:
Determination of the full complement of PCNA interactors, and how this is modified upon replication stress (Simon Cooper – BBSRC funded). This project uses affinity purification and high throughput bimolecular fluorescence complementation (BiFC) screens to identify and characterise novel PCNA interactors.
Dynamics of PCNA interactions at replication forks (Shiphali Shetty – CRUK funded). This project uses fluorescence resonance energy transfer (FRET) to monitor protein-protein interactions in real time in living cells.
Structure-function of PCNA in replication and repair (Helen Chambers – CRUK funded). This project is investigating how different mutations of PCNA affect its role in diverse cellular processes.
PCNA involvement in epigenetic inheritance (Diana Vallejo – funded by the Generalitat Valenciana). This project uses a combination of protein biochemistry and Drosophila genetics to investigate the role of PCNA in coordinating the transmission of epigenetic states during DNA replication.
Substrate identification for protein methyltransferases (Lucie Maingot - funded by the Cambridge Cancer Centre (in collaboration with Chris Abell)). This project involves the design and synthesis of S-adenosyl methionine derivatives to label methylated proteins in vitro and in vivo.