RESEARCH
Running with Scissors: Jamie Gagnon Newly-appointed Mario Capecchi Chair is using new technologies to understand how embryos develop.
genetics,” Gagnon says, “is that zebrafish are now genetically accessible model of all vertebrates, including humans which share 70 percent of genes with fish.”
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The impulse for Gagnon’s current work in vertebrate lineage and cell fate choice happened in Northern Maine, during a winter-mountaineering trip with his friend and fellow researcher Aaron McKenna whom he met while they were undergraduates at Worcester Polytechnic Institute in Massachusetts. There in the wilds, not far from Vermont where Gagnon grew up, ensued an extended conversation between the two which started to form a deeply complex but exciting research question.
“Before CRISPR,” says Gagnon whose interest early on had been more in engineering than biology, “we were all using the earlier generation of genome editing tools. Even so, we were able to determine that after making a mutation in a cell, when it divided, the change that had been made was inherited.”
“If we want to study how embryos grow, we have to do it in a living animal,” Gagnon remembers acknowledging to McKenna. “We knew we needed to do it [research] in live animals, complete and whole. I couldn’t shut up about it for several days,” he says, smiling. “Everyone was mutating genes.” It seems that at the time, and perhaps still to this day, ‘Let’s break a gene and see if you’re right about what it does’, was pro forma.
ne could argue that the age of genomes is divided between before CRISPR-Cas9 and after CRISPR-Cas9 (commonly referred to as just “CRISPR”). As a Harvard post-doc studying the genes involved in embryo development, James (Jamie) Gagnon remembers in 2012 that “pivotal moment” when these “really nice pair of scissors now easy to make” came on the scene.
The new “scissors” rapidly scaled up genome editing, allowing researchers to more easily alter DNA sequences and modify gene function. At the time CRISPR was inspiring others to move from the research model of smaller organisms like the C. elegans, a transparent worm made up of approximately 1,000 cells, to much larger ones like zebrafish. “The power of 12
Photo: Matt Crawley
Instead, the developmental biologist (Gagnon) and the computational researcher (McKenna) decided to pick up where others had ended (and published), using technology in a creative way to mark cells with a genetic barcode that could later be used to trace the lineage of cells. The two were
