Sliding clamps featured heavily in our work. These ring shaped proteins slide along DNA and tether the majority of DNA polymerases and many DNA modifying and repair factors enable temporal and spatial regulation. The bacterial beta clamps and archaeal and eukaryotic PCNAs are structural homologues, despite low sequence identity.

Our work in E. coli focussed on the potentially mutagenic translesion DNA polymerases. Inappropriate regulation of these enzymes has been implicated in cancer initiation in humans and in the adaptation of bacterial pathogens. It is therefore important to understand the molecular basis of this regulation to develop novel therapeutics. The sliding clamps provide a common source of regulation.

We also employed a halophilic archaeal model system to shed light on regulation in eukaryotes. Additionally, understanding how these extremophiles survive in very high salt conditions and how their proteins have adapted is of interest to the biotech community.

We exploited innovative approaches to promote complex crystallization for further study.