Xinnian Dong chose to study plants in part because she's uncomfortable with the alternative. She is fascinated by immunology, but the more obvious research models were not a good fit. "I feel squeamish working with animals, so I think plants are perfect," she says. Thanks to that decision 20 years ago, today she is a pioneer in understanding how plant immunity works and spends her days probing the detailed mechanisms of plant–pathogen defense in her lab at Duke University.
As a high schooler applying for college in China, Dong had to pick a major. She was attracted to social science, but her father discouraged her. The Cultural Revolution had just ended, and he'd had a difficult time as an economist. "My dad told me that molecular engineering and molecular biology would be the future," she says. So she settled on microbiology and fell in love with it. Molecular Genetics, An Introductory Narrative, by Gunther Stent and Richard Calendar, became her favorite textbook. She came to the United States for a Ph.D. in microbiology at Northwestern University. After earning her Ph.D., she made the switch to plants so she could study immune systems.
Understanding the plant immune system may help scientists figure out ways to combat crop diseases, which are a major problem for farmers. But when Dong started as a postdoctoral fellow in Frederick Ausubel's lab at Harvard in the late 1980s, the field of plant immunology was at such a basic level that she had to start by finding a model system she could use. She and colleagues searched for pathogens that can attack Arabidopsis thaliana, a weedy relative of broccoli that is used widely for research, and came up with a species of Pseudomonas. Others in the field have since adopted this plant–pathogen pair as one of the most popular models for studying how plants defend themselves and how infection works.
Dong has worked much of her career to understand a phenomenon called systemic acquired resistance. Scientists originally described in the 1960s that when a plant was infected with a pathogen, even in just one area of one leaf, the entire plant became resistant to many pathogens. The chemical messenger that induced this plant-wide resistance was salicylic acid, a close relative of aspirin.
In 1992, when Dong started her own lab at Duke, systemic acquired resistance was found to be associated with the activation of a suite of antimicrobial genes by salicylic acid. Using these genes as markers, Dong found a particular signaling gene, named NPR1—she and her colleagues liked National Public Radio—that is involved in receiving the message from salicylic acid.
Dong has continued working on NPR1. Her studies of the protein's behavior in cells have helped make salicylic acid signaling one of the best understood pathogen-defense pathways in plants. She has revealed that NPR1 actually controls several types of immune response—much like the immune regulatory protein NF-κB, which is well studied in animals. She has worked out the details of how NPR1 activates genes in response to salicylic acid, a signal that is received in the cytoplasm of the cell. NPR1, she found, waits in the cytoplasm, inactive, until salicylic acid triggers its move to the cell's nucleus, where it activates genes related to resistance.
One of the more surprising discoveries to come out of Dong's lab is that the Arabidopsis immune response varies during the day. Her team came across this phenomenon as they studied which genes were turned on in plants that were resistant to disease. They were surprised to find that some genes were associated with a regulatory element that is also linked to the plant's circadian clock. "Then we went back to look at the time course of these genes and, sure enough, they have this circadian rhythm," she says.
It turns out that the pathogen they were studying, Hyaloperonospora arabidopsidis, normally releases its spores at dawn—and that's when the resistance genes were active. If she put spores on a plant at another time of day, it would get infected. "Of course, this will make studying plant defense much more difficult, because you have to take a time series. That is expensive, time-consuming, and technically challenging," she says. The work requires sophisticated equipment and much more manpower—something her HHMI-GBMF appointment will help with.
Another new research interest is studying how the cell's machinery for repairing DNA damage is involved in plant defense. Dong knows these genes are active when a plant is under attack, but she hasn't been able to work out why. "We have tried hard to make this connection, but the conventional methods we use are just not sensitive enough," she says. As an HHMI-GBMF investigator, she hopes to use high-throughput analysis to get an answer. "I'm so excited about these two new projects," she says.