Epigenetics and Ageing

Environmental factors such as diet and lifestyle can alter the way in which our genes are expressed. This is achieved primarily through chemical modifications on DNA, RNA and histones. The study of how these modifications interact with the environment to bring about gene regulation is known as epigenetics. There is increasing evidence that epigenetic mechanisms contribute significantly to longevity and ageing control.

 

Our lab is particularly intrigue by two families of epigenetic enzymes that are able to directly reverse the methylation marks on histones and on DNA/RNA, namely JmjC histone demethylases and nucleic acid demethylases, respectively (Figure 1).

 

Over the years, we have identified a range of selective probes that could modulate the epigenetic processes mediated by these enzymes. We are currently applying these probes to help us understand the role of the various enzymes in ageing and the molecular mechanisms involved. It is hoped that this work will lead to the discovery of novel therapeutic targets to combat ageing-associated diseases and, even possibly, ways of delaying ageing.

 

estherwoon-epigenetics-and-ageing-fig1estherwoon-epigenetics-and-ageing-fig2

Selected publications

  1. Singh, N.: challiday, A.; Thomas, J.; Kuznetsova, O.; Baldwin, R.; Woon, E. C. Y.; Aley, P.; Antoniadou, I.; Sharp, T.; Vasudevan, S.; Churchill, G.A safe lithium mimetic for bipolar disorder. Nature Communications, 2013, 4, article no. 1332, doi:10.1038/ncomms2320.
  2. Chowdhury, R.; Yeoh, K. K.; Tian, Y. M.; Hillringhaus, L.; Bagg, E. A.; Rose, N. R.; Leung, I. K. H.; Li, X. S.; Woon, E. C. Y.; Yang, M.; et. al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO reports, 2011, 12, 463-469.
  3. Rose, N. R.; Woon, E. C. Y.; Kingham, G. L.; King, O. N. F.; et.al. Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches. Journal of Medicinal Chemistry 2010, 53, 1810‑1818.
  4. Woon, E. C. Y.; Demetriades, M.; Bagg, E. A. L. et. al. Dynamic combinatorial mass spectrometry leads to inhibitors of a 2‑oxoglutarate dependent nucleic acid demethylase. Journal of Medicinal Chemistry 2012, 55, 2173-2184.