About 30 years ago, a young geneticist in Boston did a seemingly simple experiment: she planted seeds and watched how they fared in light or darkness. First, though, she soaked the seeds in a solution with a DNA-damaging chemical. She hoped that a few of the induced flaws might serendipitously land in genes that govern how young shoots respond to light – a core plant function essential to life on Earth.
Thousands of treated seeds went onto Petri dishes and into an incubator. To create dark conditions, the researcher, Joanne Chory, wrapped the plates with foil. A week later, she found the vast majority of seedlings growing long, spindly, white, and leafless. As expected, they’d developed in a so-called etiolated manner, as plants typically do when starved of light.
Chory investigates how the environment affects plant form and size. Shown here are two plants growing together in a high light and drought environment. Credit: Joanne Chory
Chory’s genetic screen focused on how light modifies the length of the primary stem (hypocotyl). In light (left) hypocotyls are short and fat, to hold up leaves. Underground (right), the seedling grows a much longer hypocotyl, in an effort to find food. Credit: Joanne Chory
Why is the hypocotyl such a good model for interpreting environmental signaling? Credit: Joanne Chory
Chory looks for subtle changes in the plant’s ability to respond to light. As light decreases, hypocotyl length increases. Credit: Joanne Chory
Chory performs her genetic screens of the tiny seeds of Arabidopsis thaliana in small growth chambers; a thousand or more seeds fit on a single Petri dish. Credit: Joanne Chory
Here, a long hypocotyl mutant stands tall in a background of short normal plants. It doesn’t take a botanist to find this mutant! Credit: Joanne Chory
Chory in 1989 looking for mutants among the Arabidopsis thaliana seedlings growing in a Petri dish. Credit: Joanne Chory
Chory selected for mutants that developed in the dark, but looked as though they had grown in the light (pink, far right). Credit: Joanne Chory
Chory performed screens for long hypocotyl mutants grown in white light. Each of these mutants is missing a component of one of the photoreceptor pathways, resulting in a long hypocotyl. Credit: Joanne Chory
Chory’s hypocotyl length screens also revealed mutants that could not synthesize plant hormones such as det2, a growth hormone. (For comparison, yucca is a mutant that overproduces auxin, another type of growth hormone.) Credit: Joanne Chory
Drawing on the genetic screens for hypocotyl length, Chory can now manipulate the size of plants to see how specific mutations affect plant growth. Credit: Joanne Chory
But a few seedlings looked different – they had leaves. White ones. “We had these mutants that, in the dark, developed like a plant that had seen light,” says Chory, her once-brown hair as pale as the sprouts in her 1980s work with the thale cress plant, Arabidopsis thaliana. Chory called the ghostly oddballs det1 mutants.
Her results stirred curiosity – and skepticism. The field’s top thinkers did not believe a single genetic glitch could thwart a plant behavior as complex and crucial as the light response. Chory’s study, published in 1989 in the journal Cell, not only showed otherwise but also forged a groundbreaking approach in plant biology: screening for mutants and identifying culprit genes in Arabidopsis to help untangle fundamental plant behaviors.
“She’s one of those who very clearly see the potential in things and knows where to put the effort,” says Fred Ausubel, who studies host-microbe interactions in his lab at Boston’s Massachusetts General Hospital, where Chory was a postdoc when she generated the det mutants. “She’s done that brilliantly throughout her career.”
Next to a whiteboard with scribbles of gene names and etiolated shoots hangs a handwritten note from a local 5th grader who heard Chory speak: “Please come again. One day I want to be just like you.”
The fruits of Chory’s labors hang all over her office at the Salk Institute for Biological Studies in San Diego, where she started her lab 29 years ago. One wall sports black-framed covers of scientific journals – Cell, Genes & Development, and more – all 19 highlighting papers from her lab. Next to a whiteboard with scribbles of gene names and etiolated shoots hangs a handwritten note from a local 5th grader who heard Chory speak: “Please come again. One day I want to be just like you.”
Sunshine streams through large, second-story windows, offering light to two botanical specimens – an orchid and a lemon lime prayer plant her administrative assistant bought at Ralph’s to replace one that was dying. For someone who’s spent decades exploring the molecular intricacies of plant systems, Chory doesn’t have much of a green thumb. “My daughter jokes that I know the insides of plants better than their outsides,” she says.
In 1997, Chory became the first plant biologist selected as an HHMI investigator. Since then, her lab team has identified and characterized many of the molecules that relay signals from phytochromes – light-sensing proteins in the cytoplasm of plant cells – to light-activated genes in the nucleus. “I can tell you in great detail how a plant gets bigger,” Chory says.
“To her, you’re not done until you can answer the question, What is the mechanism?” says Jennifer Nemhauser, a former postdoctoral fellow of Chory’s who now heads a lab at the University of Washington, Seattle, as an HHMI faculty scholar. “That’s what drives her.”
Born to Lebanese parents, Chory – a baby boomer – grew up north of Boston as the third of six children. Four were boys, and Chory credits them with helping her develop a thick skin. “They toughened me up,” she says, recalling childhood forts and snowball fights. “No one at work said anything nearly as mean as those guys. They taught me to understand male personalities. I could get right in on that banter.”
Chory didn’t know what she wanted to study when she started as an undergraduate at Oberlin College in Ohio. “I was kind of a late bloomer in science,” she says. But then she took genetics. “All this heritability stuff – you can see it around you, just looking at people. It wasn’t as abstract as differential equations.”
After earning a bachelor’s degree in biology with honors, Chory went on to the University of Illinois where she completed a PhD studying photosynthetic bacteria with Samuel Kaplan. (“He called me ‘Chory,’” she says of her thesis advisor, also an ex-Marine.) She flourished there and during her postdoc with Ausubel. She loved being free to think and work on her own in labs led by hands-off investigators, and she runs her own lab with a similar approach. “Let people know you like and respect them, but expect them to do things on their own,” she says.
Even as a trainee, Chory worked with uncustomary thoroughness. Ausubel still recalls Kaplan’s recommendation letter, one of hundreds he’s read over the years. “He said she would do her work and then hand him a fully fleshed-out manuscript that he could basically submit to a journal,” Ausubel says. “Not many postdocs can do that, let alone grad students.”
Before choosing Ausubel’s group for her postdoc in 1984, Chory visited three plant labs and three fruit fly labs. Drosophila science was buzzing, the field glutted and competitive; the plant world seemed inviting. “I thought, ‘That field’s wide open. I could do something important there,’” she says.
At a time when most plant biologists focused on maize, wheat, and other food crops, Chory saw potential in Arabidopsis – an economically insignificant plant that has since become a mainstay of genetics research. “Arabidopsis was in no way established as a real model system at that point. She was taking a leap of faith,” says Steve Kay, a molecular geneticist at the University of Southern California, Los Angeles.
Kay has collaborated with Chory on about a dozen papers and considers her a close friend. But, he says, “it wasn’t always that way.” The two met in the mid-1980s as postdocs – she at Mass General, he at the Rockefeller University in New York – each keen on applying tools of molecular genetics to figure out how light regulates growth in plants. At a 1987 meeting, Kay laid out his approach: find light-responsive genes; identify DNA stretches called promoters that regulate transcription of those genes; use those fragments to fish for transcription factors that bind the promoters; and, finally, work backwards toward the light-sensing phytochromes.
Afterward, as Kay recalls, Chory piped up, “Well, that’s really an old-fashioned way to do things. We’re going to do it much better than that with genetic screens.” Later, he says, “She gave an amazing talk that made me incredibly jealous.” Chory’s tack was simple: Induce mutations; grow the seeds on dishes, and look for plants that grew short and fat with big leaves in the dark instead of tall, leafless, and spindly. Then identify the mutated genes, figure out what they do, and assign them to a molecular pathway.
“I don’t think any of us had thought to look for a plant that grew in dark the same as it would in light,” Kay says. “It was a stroke of genius.” Joe Noel, another research collaborator and HHMI investigator at Salk, agrees. “This happens a lot in science. You see something and go, ‘Oh, man, why didn’t I think of that? That’s just so simple,’” he says. “We didn’t, because it is so simple.”
Chory analyzed her det1 mutants and discovered they have a glitch in a DNA-binding protein that blocks genes needed for leaf development. Without that block, leaves sprouted in darkness. She found other mutants, too, with similar traits but involving a different gene. These det2 mutants led her lab to stumble onto a whole new class of hormones – brassinosteroids.
The det2 gene encodes a plant enzyme whose mammalian counterpart, 5α-reductase, helps convert testosterone into a more active form. Plants need their version of this enzyme to synthesize a compound, called brassinolide, found originally in Brassica napus mustard plants. In 1979, researchers purified brassinolide and showed they could add it to other plants and make them grow bigger. Chory predicted that adding brassinolide to her developing det2 seedlings should erase their defects.
The trouble is that brassinolide is tricky to synthesize. But one researcher had managed to do it, and by a stroke of luck, this man – the late chemist Trevor McMorris – worked across the street at the University of California, San Diego. Chory and postdoc Jianming Li, who now heads a lab at the University of Michigan, took a five-minute walk to the McMorris lab, left with a vial of freeze-dried powder, dissolved it, and later that same day added it to their det2 plants. On the first try, the mutants were rescued.
Linking the light response to brassinosteroids was a breakthrough, and not only in the plant realm. At the time, scientists knew that mammalian steroids hook up with receptors within the cell, and the receptors then go into the nucleus to switch genes on or off. But Chory discovered that brassinosteroids can act without even entering the cell, by binding to membrane-spanning proteins. “It was a complete paradigm shift in our understanding of how organisms generally respond to small molecules like steroids,” says Noel.
Good times and hard knocks
The lives of Chory and her husband, Stephen Worland, changed forever with the adoption of their daughter Katie and, three years later, their son Joe. Each came from South Korea at about four months of age. Now they’re both in college. “The past 22 years have gone by like a blink of an eye,” Chory says.
Life took an unwelcome turn in 2004, when her children were in kindergarten and 3rd grade – Chory was diagnosed with Parkinson’s disease. When she told the lab, Chory didn’t tear up, but spent time consoling many who did. “When you see your idols struggle with something so unfair and seemingly out of the blue, it rocks you to your core,” says Nemhauser.
Chory’s lab group recently threw a party to celebrate her 60th birthday, attended by colleagues, friends, and family, including husband Stephen Worland, daughter Katie, and son Joe. Credit: Joanne Chory
Chory and her siblings. From left: Paul, George, Chory, Mary Ann, and Michael. Missing is brother Billy, who passed away at the age of 22. Credit: Joanne Chory
Medications kept the disease at bay for about a decade. Symptoms resurfaced several years ago, but Chory hasn’t lost her sense of humor. One time, at a 2014 meeting at HHMI headquarters in Maryland, her body began to rock and knocked her to the ground. The next day, before her talk, she told her colleagues, “Given my behavior from yesterday, feel free to fall out of your chair if at any moment you disagree with what I’ve said.” Her sense of humor trickles out through understatement. “You can be having a serious conversation and then she’ll drop a joke, but it’ll be in the same tone as everything else,” says Jesse Woodson, a staff scientist at Salk who initially came to Chory’s lab as a postdoc.
In 2015, after the Parkinson’s drugs quit working, Chory had a surgical procedure called deep brain stimulation – a battery-powered implant now sends electrical pulses to the parts of her brain that control movement. Relief came immediately but, as Chory explains, “it’s a tricky device to use because the disease keeps progressing. It’s a constant game of tweaking the Parkinson’s drugs and dialing up the device.” She still puts in a full-time stint in the lab every day, but because she likes to be near her neurologist, she travels less.
One of her last long-haul trips was to Canberra, Australia, in 2013, where she spoke to young researchers about how to be a successful woman scientist. To her, traditional measures of success weren’t what mattered most. Awards, election to scientific societies, early promotion, a big raise – all very nice. But, she says, “For me, success is, Was I a good mentor to those who chose to train with me?”
Chory has by now mentored more than 100 graduate students and postdocs, and many came back to Salk for her 60th birthday symposium last spring. “It was really nice to see all these people had gone off and had their own successful careers. It made me think, ‘When I’m in my 60s, that’s what I want,’” says Julie Law, an assistant professor at Salk. “One person can’t do it all, but you can seed it. She seeded the field.”
Chory closed her Canberra talk with why it’s hard to break the gender barrier in science, and tips on how to get noticed as a scientist. State opinions, she said. Give great seminars. Ask questions at meetings. Work hard. It’s advice grounded in Chory’s own challenges and triumphs.
“I’ve grown up hearing her struggles about being a woman in a male-dominated field,” says her daughter, Katie Worland, a senior psychology major at Ohio Wesleyan University. Worland remembers her mom telling the family over dinner, “‘This man spoke over me today’ – little things like that.” But, she adds, “She’s able to brush things off that a lot of people would take personally.”
Nowadays, Chory and her colleagues want to use everything they’ve learned about plant hormones and growth to create the ideal crops – stress- and pathogen-resistant perennials to help sustainably feed the predicted 10 billion people who will inhabit Earth by 2056. The idea arose last fall when Salk's president Elizabeth Blackburn convened a group to come up with initiatives to solve 21st-century problems, climate change among them. After the meeting, Chory rallied Noel and other Salk colleagues – HHMI Investigator Joe Ecker, Wolfgang Busch, and Law – for a huddle.
“Joe Noel reminded us that, on the way to feeding the world, we could do a lot of things with plants,” Chory says. Plants take the greenhouse gas carbon dioxide out of the air and “fix and sequester” it – that is, turn it into biomass. The Salk team is using its mechanistic know-how to create this novel crop and is trying to raise $25 million from corporations, philanthropists, venture capital, and institutional funds.
“Maybe it’s time to be more global,” Chory says. “Maybe it’s time for me to let go of my studies on light signaling and just really figure out how to save the planet.” ■
Story by Esther Landhuis
Photography by Brad Torchia
Banner title art credit: Emmanuel Boutet/Wikimedia