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Ryan Lister: Epigenomics and the Control of a Genome

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Title: Postdoc, Salk Institute
Education: PhD, The University of Western Australia, 2006
Recommended by: Joe Ecker, Salk Institute

The genome contains a lot of information — information that organisms must regulate to ensure that the proper genes are expressed or silenced at the right times. Understanding how organisms keep this tight regulation under control is what drew the Salk Institute's Ryan Lister to study the epigenome.

By combining bisulfite and shotgun sequencing with next-gen tools, Lister and his colleagues have figured out the methylation state of nearly every cytosine. First, they applied this approach to the Arabidopsis genome to determine how methylation differs across various regions. Once they'd established their protocol in Arabidopsis, the researchers turned to the human genome. They analyzed the methylation status of human embryonic stem cells and fibroblasts and found something surprising — non-CG methylation. "This type of methylation is well-known, well-established in plant genomes and ... we came to the human genome with open eyes as to what could be there," Lister says.

However, working with such small systems can be a challenge, Lister says. Hopefully, he adds, there will be technological advances that will enable single-cell analysis. When asked what sort of magical tool could help his work, Lister jokes that he would want "a machine to shrink and teleport me into a cell to ride a DNA methyltransferase" so he could get a good picture of what's actually going on.

Looking ahead

Currently, Lister says that researchers can make detailed maps of where methylation exists across the genome, but there is not yet an understanding of the mechanism through which a change in that methylation state leads to disease. To find that, he suggests an iterative process of "generating each data set and then figuring out what molecular mechanisms are governing the patterns, and then analyzing how they operate though the whole genome — that I think will help us to more accurately understand the data that we produce."

Papers of note

The study of the Arabidopisis methylome appeared in Cell in 2008, and Lister says that's the paper he's most proud of. "That, perhaps because it was performed in plant, didn't receive as wide attention as the follow-up paper, which I published on methylation throughout the human genome," he says. That second paper appeared in Nature in 2009.

And the Nobel goes to ...

If he gets his magical tool, Lister says he should win the Nobel for "the first circumnavigation of the nucleus while riding a protein."

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