Science at the Shine Dome 2010
Symposium: Genomics and mathematics
Friday, 7 May 2009
Professor Susan Clark
Susan Clark has a highly acclaimed international reputation for her pioneering work in mammalian epigenetics. Susan heads the epigenetics research program at the Garvan Institute of Medical Research in Sydney. She graduated in 1982 with a PhD in biochemistry at the University of Adelaide and then spent ten years in the biotechnology industry before returning to basic research in gene regulation in 1992.
Susan’s studies over the last sixteen years have initiated profound questions about the importance of epigenetics in early development and in disease, especially in cancer. She has made extensive ground-breaking discoveries relating to DNA methylation patterns in normal and cancer genomes, which have led to new tests for early cancer detection. The techniques she pioneered in the early 1990s, including bisulphite sequencing, have revolutionised and now underpin a new era in epigenetics research.
Susan has a number of awards, including the RPAH Research Medal in 2002, Julian Wells Medal in 2003, Ruby Payne-Scott Award for contribution of women in science in Australia, ‘Biochemisch Analytik Preis’ for outstanding contribution for methylation analysis in 2004, and was elected a Fellow of the World Technology Network for Biotechnology in 2006.
Epigenetics and genetics: Discovery of layers of change in the cancer genome
Despite the completion of the Human Genome Project we are still far from understanding the molecular events underlying epigenetic change in cancer. Even though it is now accepted that tumour suppressor genes, with CpG island-associated promoters, are commonly hypermethylated and silenced in cancer, and repeat regions are commonly demethylated and genes activated, we do not understand what triggers this process or when it occurs during carcinogenesis. Epigenetic gene deregulation has always been envisaged as a local event silencing discrete genes, but recent data indicate that large regions of chromosomes also can be coordinately deregulated. To determine the propensity of genes deregulated in domains in cancer cells, we have integrated in vivo gene expression profiles from clinical samples and epigenome tiling arrays, copy number arrays and next generation sequencing to map DNA methylation and histone modifications. We find that in addition to regional genetic changes, adjacent genes are also commonly changed to the same epigenetic silencing state, by replacement and reinforcement of either active or repressive histone marks, implicating a deregulation of the epigenome in domains that span multiple genes.
