Graduate Research Prize Winners 2009
I obtained a HND in Applied Biology from the University of the West of England in 1993, and I was then employed by Oxford Glycosciences from 1994 to 2003, an Oxford University spin-off biotechnology company. Here I was initially responsible for the production of sequencing grade enzymes for glycoprotein analysis. Later I moved into the Proteomics Method Development Group where I was involved in developing new technology platforms for analysis of complex protein mixtures, e.g. blood serum. Finally, I worked in the Antibody Therapeutics Group where I was involved in research into the development of pharmacological antibodies.
In 2003 I moved to the Structural Genomics Consortium (SGC) at the University of Oxford, where I was given the opportunity to study for a D. Phil in the Nuffield Department of Medicine and Wolfson College. I was interested in working for the SGC as I could increase my knowledge of protein production/purification and broaden my horizons in structural biology.
I was supervised by Professor Udo Oppermann, who headed the Oxidoreductase Research Group in the SGC. I became interested in the 2-oxoglutarate dependent oxygenases, in particular the exciting subfamily of proteins thought to be histone demethylases. The discovery of this group of enzymes has caused a radical revision of thinking about histone methylation and its implications for epigenetics, since methylation had long been considered a permanent post-translational modification. My research on these proteins led me to crystallise and obtain the structures for 5 JMJD2A complexes, a histone H3K9 and H3K36 demethylase. These structures enabled us to propose a mechanism by which substrate specificity is attained. Later I was also able to obtain structures of JMJD2A and JMJD2E in complex with the inhibitor 2,4-pyridine dicarboxylic acid (2,4-PDCA).
I am now a post-doc on a 4-year Wellcome Trust grant to research chemical probes for proteins in epigenetic signalling at the SGC. These studies involve the development of small chemical inhibitors of several classes of proteins involved in modulating epigenetic responses. It is envisaged that these probes will help to enhance the validation of protein targets for drug discovery purposes.
- Ng, S. S., K. L. Kavanagh, et al. (2007). "Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity." Nature 448(7149): 87-91.
- Rose, N. R., S. S. Ng, et al. (2008). "Inhibitor scaffolds for 2-oxoglutarate dependent histone lysine demethylases." J Med Chem 51(22): 7053-6.
- Ng, S. S., W. W. Yue, et al. (2009). "Dynamic protein methylation in chromatin biology." Cell Mol Life Sci 66(3): 407-22.
Overview of the JMJD2A structure in complex with a synthetic histone H3 lysine 9 tri-methylated peptide (PDB code 2OQ6).