It wasn't exactly kick the can or red rover, but there was one game Sheng Yang He loved to play as a kid growing up in rural China: pick the bollworms.
"Our village was very small, only about 300 people, and surrounded by cotton fields and rice fields," He recalls. "In elementary school, we would all line up in the cotton fields and go through the rows to pick out cotton bollworms that drill holes in the cotton boll, and we'd compete to see who got the most caterpillars." There was no prize for collecting the most worms, but the teacher announced the winner, and "recognition was very good," He says.
Decades later, he still wins praise for his crop protection efforts with research on plant pathogens that also has implications for human health. His most significant discoveries have resulted from a willingness to strike out in new directions, says He, a professor at Michigan State University. That tendency emerged early in his career when, as a postdoc and young faculty member, he dared to veer away from the area of research most budding plant molecular biologists were pursuing in the 1990s.
"Most of my colleagues were trying to understand how plants defend themselves against disease, the molecular basis of plant resistance. But I thought the opposite—why plants are susceptible to disease," He says. "Looking back, that was a good decision, because it turns out that studying the molecular basis of plant susceptibility is quite relevant to human disease. Many of the mechanisms that bacteria use to affect susceptibility in plants are also used by human pathogens."
Much of He's research has centered on a bacterial weapon called the type III secretion system (T3SS). Plant scientists have known for years that most bacteria secrete disease-promoting proteins, but conventional wisdom held that those proteins affected host cells from the outside. He made the breakthrough discovery that some of these proteins act inside plant cells and went on to describe part of the needle-like structure bacteria use to deliver the proteins into plant cells.
When he joined the faculty at Michigan State in 1995, He set out to learn what the injected proteins do. "They must be doing something to make plant cells susceptible" since the cells don't die immediately, he reasoned. Sure enough, his group found that several of the proteins suppress the plant's immune response. This created such a stir that many scientists began to study susceptibility, and now it is a fertile area of investigation. It's a hot topic in human health research as well; parallel studies have shown similar immune suppression by human pathogens, including Yersinia, which causes plague.
Another significant discovery from He's lab involves plant stomata—tiny, mouth-like pores that open and close to regulate the exchange of carbon dioxide and water vapor. Typically, the pores open during the day and close at night; when they're open, disease-causing microbes can sneak in. Plant researchers had long assumed that stomata simply stood passively by when this happened, but He's group found that stomata sense invaders and close in response, thus playing a part in the plant's immune response.
Some bacteria have outwitted the system, though; they produce toxins, such as coronatine, that force the pores to reopen and let them in or they find other ways to enter the plant. Coronatine is interesting in its own right, not only for playing a role in infections but also for mimicking the plant hormone jasmonate. With its studies of coronatine, He's group was able to make major contributions to the recent discovery of the components of the jasmonate receptor complex, which regulates several important areas of plant biology, including fertility and defenses against pathogens and insects.
He plans to keep probing pathogenesis mechanisms, the stomata-based defense system, and the role of coronatine and jasmonate in plant disease, but as an HHMI-GBMF investigator he will also have the freedom to explore new territory, once again forging his own path.
One new line of research is aimed at thwarting the T3SS, that fiendish delivery system for infection-promoting proteins. "The system is so important … wouldn't it be cool if we could inactivate it?" He asks. Many research groups already are screening libraries of chemical compounds, hoping to find some that inhibit T3SS, but He is taking a different tack: searching for natural inhibitors that plants use to defend themselves against T3SS. To that end, he plans to study a broad range of plants, including some that are used as Chinese herbal medicines.
This would bring He full circle: from protecting cotton plants with his bare hands to using sophisticated scientific tools to understand how Chinese plants protect themselves against disease.