It’s already been a great year for plant scientist Joanne Chory, and 2011 isn’t half over. On May 20, the Salk Institute professor was named a member of the Royal Society. On June 12, the journal Nature published Chory-led research on an important plant molecule called BRi1. The article’s abstract is free, the entire article is behind Nature’s paywall.
Chory and colleagues determined the atomic structure of the molecule, a steroid hormone receptor. With that knowledge, they discovered that the receptor acts differently from that of animal steroids in delivering its message from the cell surface to the cell interior.
Joanne Chory
“Our genetics studies previously showed that unlike animal steroid receptors, which bind steroids inside cells, plant steroid receptors are membrane proteins, a completely different class of protein,” Chory said in a Salk press release. “Now that we know the precise contacts made between the steroid and its receptor, we can propose how the BRI1 receptor works.”
Chory, holder of the Howard H. and Maryam R. Newman Chair in Plant Biology,, has helped establish that plants use steroid hormones much in the same way as animals to, such as to regulate growth. The similarities mean her research may have implications for how steroids work on animals and humans, and may help develop faster growing, more productive crops.
A molecule of brassinolide (yellow wire model) binds to the extracellular domain of the receptor (in light-blue). Binding ultimately causes phosphorylation of the receptor's cytoplasmic kinase domain (in dark blue), thereby transducing the signal across the membrane. Image: Courtesy of Michael Hothorn and Jamie Simon, Salk Institute for Biological Studies.
Michael Hothorn, Ph.D., a postdoctoral fellow in the Chory lab, was the study’s first author. Also contributing were Youssef Belkhadir and Tsegaye Dabi of the Chory lab, Joseph Noel of Salk, and Marlene Dreux of The Scripps Research Institute in La Jolla.
More from the press release:
“Michael’s structural work is the final brick in the wall, ” says Chory, noting that BRI1 serves as the prototype for a large class of similar proteins expressed in plants. Interestingly, BRI1 is an exception in that family: while its job is to relay growth-promoting signals, many of its look-alikes actually stimulate immune responses in plants, protecting them from insects, worms or bacteria. Whether BRI1’s sibling receptors display such a twisted structure opens new avenue of investigation.
Many common herbicides were designed to mimic the structure of plant hormones. “Because brassinosteroids are hormones, knowing the structure of their receptor will allow us to rationally design herbicides that could block interaction between hormone and receptor,” says Chory. “This would enable us to manipulate how fast plants grow and how large they become-traits that are important in crops that must soon feed 10 billion people.”
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Here’s a profile of Chory I wrote for the North County Times published Sept. 14, 1997:
Salk scientist unlocks life’s mysteries with plants
By Bradley J. Fikes
You’d expect a research scientist at the Salk Institute to have laboratories, freezers and cell dishes. But a greenhouse?
Located at the institute’s west end, the greenhouse is the territory of plant biologist Joanne Chory. The Del Mar resident shunned the glamour of researching cancer, AIDS or other human diseases to focus her life’s work on an unprepossessing little weed called Arabidopsis thaliana.
But Chory’s lab has made the biomedical world do a double-take. The researchers found that plants use steroid hormones via certain cellular “receptors” presently unknown in animals. If those receptors exist in animal cells, it could lead to entirely new treatments for human diseases.
In May, Chory was named a Howard Hughes Medical Institute investigator, a title that brings substantial research money in addition to prestige. She’s only the second plant biologist to receive HHMI funding.
On Sept. 5, Chory and lab colleague Jianming Li published a scientific paper in the journal Cell about brassinolide, a plant steroid that regulates growth. They found evidence for the existence of a gene that makes a receptor for brassinolide. A receptor is a substance in the cell membrane that allows the hormone to work.
It’s sweet vindication for Chory after a decade of research — and for other plant scientists.
“Plant research is just not funded so well, and there’s not nearly so many people who do it,” Chory said. “It’s not going to have that high-impact kind of science about it as someone who discovers a gene involved in obesity.”
That may be changing, said Anthony B. Bleecker, an associate professor in the botany department of the University of Wisconsin.
“The animal scientists are now very interested in the steroid aspect of plants that she’s uncovered,” Bleecker said. “These are spinoffs you could never predict from her starting point.”
New evidence in modern molecular biology and genetics increasingly says that plants and animals share many fundamental traits, retained since their evolutionary paths split an estimated 1 billion years ago. Genes and enzymes found in plants may be present in identical or nearly identical forms in animals.
“We’re finding that, surprisingly, at subcellular levels and processes, plants are really not that different from animals,” Bleecker said.
Beneath their placid exteriors, plants are very active chemical factories, Chory said.
“Plants are very good at making all sorts of small molecules to defend themselves because they’re just stuck there — something comes along and chomps on them, and they make a response,” Chory said.
Chory didn’t set out to make any such sweeping discoveries. She chose to study arabidopsis because it is easy to work with — it has relatively few genes, is easy to grow and has a short life cycle. It’s the botanist’s version of a guinea pig or fruit fly.
As a “postdoc,” or postdoctoral student, Chory studied in the genetics department at Harvard Medical School. For a while, the lab she worked in was located in Massachusetts General Hospital, which caused some incongruous scenes for the budding plant researcher.
“We would take out little carts of plants in the elevator with patients, because the greenhouse was on the roof,” Chory said.
“Many of the people in the hospital never could figure out why they had greenhouses on two of the buildings. But it was the view of the genetics department that you should do genetics on different organisms, because you never know where the breaks are going to come from.”
After completing her postdoctoral work about 10 years ago, Chory applied to a number of research institutions, including the Salk Institute. After acceptance, she moved to San Diego along with another person — her husband, biochemist Stephen Worland. With San Diego’s growing biomedical industry, they reasoned, he wouldn’t have much difficulty finding a job.
They were right; he was hired by La Jolla-based Agouron Pharmaceuticals. The couple live with their 2-year-old adopted daughter, Katherine.
Getting used to San Diego was difficult for Chory.
“I didn’t like it so much when I first moved here. It’s just different,” Chory said. “I was always in a lab where you have a lot of peers and buddies. All of a sudden you have your own lab, and you’re there by yourself for a while. There’s a lot of adjustments to make, and you have to work really hard.”
The work started with an elementary question: How do plants respond to light?
Chory’s team studied the problem genetically, searching for mutants whose response to light was disordered. They found mutants that were “blind” to certain wavelengths of light, mutant seedlings that grew in the dark as if they were in the light, and other variants. Among the genes they found was one very similar to a gene involved in animal steroid metabolism, a hint that exploring plant genetics would have implications for animals.
Chory picked up on earlier research that showed that a steroid called brassinolide could make plant cells elongate. Some of the mutants Chory’s team had found were much smaller than normal. Could brassinolide restore the mutant to its normal appearance? The answer was yes — descendants of stunted plants given brassinolide were “rescued” and looked completely normal.
Continuing their work, the researchers found they could insert a brassinolide-making gene into a mutant plant and grow normal plants from it.
“First we create the disease, in a way, by making a mutant; then we can do gene therapy because we can correct it,” Chory said. “That’s usually the proof in principle that we’ve cloned the right gene.”
It sounds simple, but Chory said the process took years.
With the second gene that codes for the brassinolide receptor, Chory’s lab is hard at work to determine how the two genes can best work together.
Chory’s researchers have already grown larger than normal arabidopsis. That’s interesting, she remarked dryly, but “nobody cares about arabidopsis being bigger.”
Working with another Salk researcher, Chory’s team found that rice yields increased when the brassinolide-making gene from arabidopsis was added to rice.
Two patents for the genes have been applied for, but Chory said she can’t take part in any commercial experiments due to her agreement with Howard Hughes Medical Institute.
“I hope some biotech company would actually do the experiment,” Chory said.
“You’re doing basic research, but you would like to see an impact from it in your lifetime,” Chory said.
