Professor Ryan Lister, Australian Research Council Centre of Excellence in Plant Energy Biology, Harry Perkins Institute of Medical Research, The University of Western Australia.
Covalent modifications of DNA and histones play critical roles in the regulation of gene expression, cell activity, development, and disease. DNA methylation is a critical layer of the vertebrate epigenome, however despite several decades of investigation, the precise roles of DNA methylation in the control of genome and cell activity are still not clearly understood. A major obstacle in deciphering the mechanistic roles of epigenomic modifications has been the inability to precisely control and change the modification states in the genome. However, genome editing technologies are now rapidly being repurposed to achieve editing of epigenomic modifications where desired in the genome, in order to elucidate the causal relationships between these modifications and genome regulation, and as artificial regulatory tools to control cell activity and identity. We employed a broadly active artificial epigenome modifying protein to achieve genome-wide manipulation of promoter DNA methylation, enabling comprehensive assessment of its effects upon transcription and histone modifications, and the stability of artificially induced methylation. Furthermore, we have developed new CRISPR-Cas9 based tools that enable highly specific addition or removal of DNA methylation at desired locations in the genome in a controlled fashion. In addition to optimizing the efficacy and specificity of these functional epigenomics tools, we have utilized them to explore the sensitivity of DNA binding proteins to DNA methylation state. Overall, recent developments in epigenome editing tools are providing new insights into the role of covalent genome modifications in regulating gene expression, and new platforms for the manipulation of cell activity and identity.
Professor Ryan Lister leads a research group investigating the epigenome, at the University of Western Australia and the Harry Perkins Institute of Medical Research. After receiving his PhD from UWA in 2005, Ryan undertook postdoctoral studies at The Salk Institute for Biological Studies in California from 2006, where he developed new techniques to map the epigenome. His discoveries include generating the first accurate maps of the human epigenome, and characterizing the complexity of the human brain epigenome. His research has yielded new insights into the composition and function of the epigenome in a variety of systems, including plants, the brain, stem cells, and developing vertebrate embryos. Having returned to UWA in 2012, Ryan’s laboratory is focused upon understanding how the epigenome patterns are established and changed, how they affect the readout of underlying genetic information, their involvement in development and disease, and developing molecular tools to precisely edit the epigenome.