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“About 20 years ago, most biomedical scientists were lukewarm on the benefits of plant research,” says HHMI investigator Joanne Chory, a plant biologist at the Salk Institute for Biological Studies.
“But we've since found that we can freely manipulate genetics in plants, making transgenic varieties. I like to say that we can actually do gene therapy in plants because the plant genome can stably integrate and express introduced genes—and that has opened the way to new molecular insights.”
This bloom has emerged, in large part, because of the model mustard plant Arabidopsis thaliana. Its sequenced genome, published in 2000, showed that mustard and humans share some important biology. At least 139 known human disease genes have homologues, or counterparts, in Arabidopsis. Even more basic, perhaps, is a shared biochemistry that makes life possible. “Like almost all higher organisms, humans and plants have much in common,” says HHMI investigator Steven E. Jacobsen, a plant biologist at the University of California, Los Angeles. “Thanks to work in a number of labs, plant research is rapidly gaining more respect.”
Jacobsen, whose lab is one of those pushing plants to the forefront, grew up on a farm in Merced, California, and had originally planned to work in plant development. As a postdoctoral fellow at the California Institute of Technology, however, he stumbled upon a set of unusual mutations that changed developing flowers. Flowers with these mutations sprouted extra male sexual organs, or stamens. Yet, sister plants, sharing the same basic DNA, remained perfectly ordinary, with the usual six stamens.
Puzzled, Jacobsen compared his mutant and ordinary plants. He found a telling difference in a key gene, called SUPERMAN, that regulates flower development. The difference—and the launch of his career—was DNA methylation. As Jacobsen's subsequent work has illustrated in detail, plant cells can turn off, or silence, particular genes by chemically attaching methyl groups to their surface. With this trick, plants regulate gene expression to control cell growth and development. DNA methylation is a primary example of what's called epigenetic gene regulation—or heritable changes in gene expression that do not modify the fundamental gene sequence.
In fact, what Jacobsen witnessed at the lab bench—the difference between ordinary flowers and blossoms bearing extra stamens—resembles a devastating biochemical process in humans: cancer. Like plant cells, human cells also methylate DNA. And some cancer cells inappropriately methylate tumor-suppressor genes in particular, effectively silencing them and allowing the cancer cells to grow unchecked.
“I realized then,” Jacobsen recalls, “that these plant mutations could give us a real genetic handle on DNA methylation, explaining the biochemistry with experiments that would be impossible to do in other models.” Key biomedical model organisms, such as the fruit fly, worm, and yeast, wouldn't cut the mustard, so to speak, because they lack the DNA methylation feature. And “experimentally reducing DNA methylation kills embryos in other mammalian systems,” says Jacobsen. “But in plants, with their built-in biological redundancy, you can knock out various genes and the plants still thrive.”