Exploring and engineering the epigenome
Much like many young teenagers, new Fellow of the Australian Academy of Science Professor Ryan Lister was a fan of Jurassic Park. Fascinated by the fact that the DNA within a cell could encode all the diverse forms and functions of mythical creatures in the fictional series, his passion went on to fuel lifelong research on understanding the information in human and plant genomes.
“The fact that this seemingly simple molecule located within us contains all the information necessary to create the vast complexity of a person or a tree,” he says, “is incredible!”
Beginning at the University of Western Australia (UWA) with a bachelor degree in biochemistry and genetics, Lister went on to complete his PhD in plant mitochondrial biogenesis.
Manipulating the epigenome to address societal challenges
Lister’s research is now focused primarily on understanding how the information encoded in the DNA of plant and animal genomes can be influenced by the epigenome.
The epigenome, a molecular code that is superimposed on the DNA of our genome, is comprised of millions of tiny chemical tags that can be added to the DNA or the proteins around which it is wrapped. It plays a critical role in regulating how the information in the underlying DNA sequence is used by a cell.
Lister looks at how different forms of these chemical tags, such as DNA methylation—a type of chemical signpost that can signal a change in the activity of a DNA segment—can be altered during development, by the environment, and in disease states. His team is developing molecular tools to precisely engineer the epigenome.
“Having the ability both to understand the roles of the epigenome and to manipulate it, means that we will be able to control cell functions with much greater sophistication,” says Lister. “This will have an important role in a diverse range of areas ranging from regenerative medicine to understanding the epigenetic basis of disease.”
Several years ago, Lister’s team at UWA along with international colleagues made a breakthrough—they discovered that the epigenome in neurons in the human brain changes enormously during childhood, suggesting that this may be important in the maturation of neurons, which is critical for both brain development and the process of learning.
But even the most exciting discoveries are not immediately euphoric. “You may realise that you’re seeing something for the first time that nobody else has ever seen, but usually it’s a bit more mundane,” he says. “You think, that’s a bit odd that it doesn’t fit what I’ve seen before. I better check that it is not a bug in the code. After a long process of checking and rechecking, you may actually find that it’s something truly new.”
Nevertheless, it’s “amazing to be a part of that process. You realise just how it creates the world of the future. [Science] is a process that no other creature in the history of earth has developed, and it’s allowing us as a life form to actually dissect and decode ourselves,” he says. “That’s life understanding life, which I find pretty inspiring.”
Lister’s earlier work had drawn up the first high-resolution maps of the human epigenome. He was able to find that the chemical signposts that comprise the epigenome differ greatly between embryonic stem cells and specialised adult cells. He also discovered that when specialised human cells were converted into adult stem cells, these reprogrammed stem cells retained a memory of the cell they once were. In 2009, his work on human epigenome mapping was rated by TIME magazine as the second most important scientific discovery of the year.
“[Science] is really the only process we have for rigorously understanding the world, the universe around us, and how it works,” he says. “Understanding problems and devising new solutions will be critical for facing the major challenges we have at this time, from diseases and pandemics through to climate change.”
Lister Lab: new insights into the function of the epigenome
Lister has established his own research group at UWA and The Harry Perkins Institute of Medical Research that has provided new insights into the composition and function of the epigenome in a variety of systems—from epigenomic reconfiguration during brain development, to plant stress response and cellular reprogramming. His research has also led the construction of new molecular tools for the precise editing of the epigenome.
At present, Lister is looking at inventing new tools to edit a suite of these chemical tags that decorate the genomes of humans, plants and other multicellular organisms. He is also seeking to explore the role of chemical tags in brain development, which could offer new insights into neurological disorders.
For Lister, science is about problem solving. He recommends a career in science to those who like to work in teams to tackle big challenges. “If you like to discover new elements of the world, how they operate, and to change people’s lives and change the future, it’s a really rewarding career.”