Professor Tony Kouzarides
Our group is interested in defining the mechanisms by which chromatin modifications function to regulate cellular processes. Our attention is focused on a set of enzymes (acetylases, deacetylases, methylases and kinases), which regulate transcription by covalently modifying histones. We would like to understand what biological processes these enzymes control and the precise role of each modification on chromatin dynamics. In addition, a number of chromatin modifying enzymes have been implicated in the genesis of cancer so we are dissecting how these pathways missregulated in cancer cells.
Histones are very highly modified. Despite their abundance, we believe that more modifications are likely to exist on histones. This complexity is probably necessary because histones integrate many signalling pathways with biological processes involving DNA manipulation. We are taking a number of complementary approaches to characterise the function of chromatin modifications. We use yeast as a model system whenever possible to define pathways. We use human cells to characterise function in higher organisms and probe connections to cancer. Mechanistic analysis of modifications is carried out using recombinantly assembled nucleosomes that are modified at specific residues.