Steve Gamblin group

Structural biology of influenza, energy metabolism and cancer

We study the structure and function of molecules involved in diseases such as influenza, diabetes and cancer. We use X-ray crystallography and NMR to determine the three-dimensional structures and dynamics of these molecules. In combination with other techniques, the data help us elucidate the function of relevant proteins and provide information for development of therapeutic approaches.

We have a long-term interest in how covalent modifications of histones, that package DNA into chromatin, regulate gene expression through epigenetic mechanisms. Polycomb Repressive Complex 2 (PRC2) is essential for the maintenance of repressive chromatin domains in early development, and its overexpression is linked with a number of different cancers. We have uncovered how the PRC2 complex is able to tri-methylate K27 on H3 in the context of existing repressive methyl marks on neighbouring chromatin, but not in the absence of these marks. We have shown that the EED subunit of PRC2 specifically recognises H3K27Me3 and that this leads to activation of the methyltransferase activity of the PRC2 complex. These collaborative studies provide the first mechanistic insight into the propagation of repressive chromatin domains, and may lead to the identification of small molecule inhibitors that could be tested for activity against certain cancers.

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Structure of EED bound to a trimethylated H3K27Me3 peptide (shown in stick representation)

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Gamblin group

Dr Steve Gamblin

Steve Gamblin

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