Research Themes:

Our research focuses on understanding the molecular mechanisms of epigenetic processes. Epigenetics is the term used to described covalent modifications to DNA and histones which constitute a set of inherited changes in gene expression, without changing the underlying DNA sequences. By developing chemical probes against the proteins that regulate these epigenetic modifications, we hope to gain a better understanding of their mechanisms and how they influence the expression of genes.

JMJD2A Substrate Peptide

Crystal structure of the histone demethylase KDM4A (atoms shown as spheres) with a histone H3 substrate peptide methylated at lysine 9 (atoms shown as sticks). Green sphere is the metal atom.PDB ID: 2OX0

Our current major research focus is histone demethylases (KDMs), a biomedically important family of oxygenase enzymes (> 20 enzymes) involved in modulating the methylation levels on histone tails. KDMs are strongly linked to many cancers and ischaemic diseases. We utilize a wide range of biochemical, biophysical and cellular techniques to study the functions of these enzymes. We have also developed a number of chemical tools for KDMs and related oxygenases. We work at the interface of chemistry, biology and medicine, and many of our projects are highly collaborative.

Maldi Spectrum

MALDI TOF mass spectra of a histone H3 peptide dimethylated at lysine 36. Black line spectrum shows how the histone demethylase KDM2A removes both methyl groups from the lysine. Red line spectrum shows the result of the reaction without KDM2A present.For more information see Williams S et al. Studies on the Catalytic Domains of Multiple JmjC Oxygenases Using Peptide Substrates.Epigenetics 2014 9(12):Online