Understanding the diverse molecular mechanisms of chromatin-targeted histone deacetylase complexes

Our genetic material, DNA, is wrapped around histone proteins to form nucleosomes which are packaged together to form chromatin. Chromatin can exist in an open state in which genes are active or a closed state in which genes are repressed. We are studying a family of enzyme complexes (histone deacetylases) that are involved in controlling the switch from open to closed chromatin. These complexes are all essential for life. We wish to understand the mechanisms through which these complexes recognise and manipulate chromatin. We will use Cryogenic Electron Microscopy to determine the three-dimensional structure of three important complexes bound to chromatin and gene-editing experiments to explore their function in cells. This research will lead to a fundamental understanding of the mechanisms by which these complexes regulate genes and may ultimately facilitate the development of novel therapeutics.