The lab studies the mechanisms that cells use to deal with impediments to DNA replication, for instance damaged DNA bases or DNA secondary structures. We are particularly interested in how replication blocks lead to changes in the DNA sequence, mutagenesis, and to changes in gene expression through localised changes in the epigenome, or epimutagenesis. These replication-dependent changes in the genome and epigenome in turn drive the aberrant behaviour of cancer cells and may contribute to abnormal development and to the clinical features of some inherited human disorders. Our projects fall into three related areas:


DNA damage tolerance and mutagenesis

We have a longstanding interest in translesion synthesis, a mechanism to replicate damaged DNA that carries with it a high risk of mutagenesis.

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Replication stress induced epigenetic instability

We explore how replication blocks caused by DNA secondary structures can lead to localised changes in gene expression.

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In vitro affinity maturation and selection

We are working to harness immunoglobulin gene mutagenesis in cell lines to select and evolve novel antibodies and other proteins.

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Due to the pandemic, the 2020 Mutagenesis GRC has been rescheduled to 2022:

June 12th - 17th, 2022. Jordan Hotel at Sunday River, Newry, Maine, USA

Chair: Julian Sale, Vice Chair: Houra Merrikh

Full details: https://www.grc.org/mutagenesis-conference/2022/

The group is part of the Division of Protein and Nucleic Acid Chemistry at the MRC LMB in Cambridge, UK. LMB provides an unparalleled environment for pursuing fundamental questions in molecular biology that will shape our understanding of human physiology and disease.

We are principally supported by the Medical Research Council, with additional current funding for group members from The Darwin Trust of Edinburgh and AstraZeneca


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