When Jeff Dangl first began to wonder how plants fight off pathogens, he didn't head to the woods and collect specimens as a field biologist might—he headed to the lab and cracked open a catalog for a microbial strains collection. It was 1987, and new genetic tools were making the flowering weed Arabidopsis thaliana an increasingly powerful research tool. Dangl, a geneticist, ordered frozen vials of microbes that he suspected might pose a threat to the weed, since they infected its cultivated relatives like radishes and cabbage, and then started mapping the fundamentals of the plant immune system that generations of plant breeders had long suspected must exist.
Plants are confronted by a daunting range of bacteria, fungi, and viruses. Communities of microbes teem above and below the soil's surface, many seeking opportunities to infiltrate a plant's cells through surface wounds, natural pores, or direct attack. Unlike animals, plants do not have armies of circulating immune cells, each trained to recognize a particular pathogen. Each plant cell must be prepared to recognize and deal with any harmful intruder it encounters. Most of the time, the plants succeed.
As a graduate student at Stanford, Dangl studied antibody function in mice, earning his degree in genetics and immunology. Those fields fueled his scientific curiosity when he moved to the Max Planck Institute in Cologne, Germany, on a National Science Foundation postdoctoral program aimed at attracting scientists trained outside the field of plant molecular biology to move into it. During nine years in Germany, including six as a group leader at the Max Delbrück Laboratory, he developed Arabidopsis into a model for studying plant–pathogen defense—and he learned to speak reasonably fluent German, having arrived knowing only how to order a beer.
In 1995, Dangl moved his lab to the University of North Carolina at Chapel Hill, where his research has revealed key elements of plants' multitiered defense system. Dangl says he looks at problems differently than many of his colleagues who trained as plant biologists. "I try not to be too caught up in the current dogma," he says, noting that his background complements that of those who have been more entrenched in plant biology throughout their careers. "I think the more oblique views a community can have bearing down on their problem, the better off it's going to be." He admits to struggling to identify a plant cell under a microscope early in his career, but his "outsider" way of looking at things has helped him generate new and unexpected ideas about how plants protect themselves.
The first line of defense for plants is a general immune response that is launched when receptors on the surface of the plant's cells detect the presence of a microbe. The receptors recognize molecules that commonly occur on microbes' outer membrane, which serve as identifiers of a potential threat. According to Dangl, plants rely on this system to prevent most of the pathogens in their environment from growing in or on their cells. Many pathogens counter this defense, however, using molecules that directly impair the immune machinery. Plants have receptors that recognize these molecular weapons, known as effectors, and activate a second-level immune response. Plant breeders have taken advantage of these protective receptors for more than a century, as they select plants that are resistant to particular diseases and pass that trait on to future generations. Dangl and other biologists began identifying and characterizing these receptors, called NB-LRR proteins, in the early 1990s. Dangl contributed to understanding NB-LRR proteins and explaining how they are activated, which has made breeding for disease-resistant plants easier.
Plants' resilience to disease remained puzzling, however. Bacteria, fungi, and insects have evolved a diverse armory of effectors to overcome plant defenses, and it seemed unlikely that plant cells were clogged with enough NB-LRRs to detect them individually. "If you have a specific receptor for all non-self molecules, you'd have a bajillion specific receptors, and you wouldn't have any room for anything else," Dangl explains.
In 2001, Dangl and his friend Jonathan Jones, a plant biologist at the Sainsbury Laboratory in the UK, proposed a more efficient strategy: instead of directly detecting pathogen effectors, immune surveyors might instead monitor the integrity of the proteins that effectors impair. He called this idea the guard hypothesis and showed that there are indeed plant receptors that guard key host proteins, mounting an immune attack when they are damaged—regardless of which effector has caused the damage.
Dangl and others have gathered evidence indicating there are about 140 different such receptors in Arabidopsis. When animal immunologists took note of the discovery, they found similarly functioning immune receptors: about 30 have been identified so far in humans (who likely need fewer because circulating immune cells are ready to catch most invaders) and 1,000 have been found in sea urchins (who have less sophisticated immune systems). "There's been a bit of a convergence over the past 10 years," Dangl notes. "It's kind of nice—it's been a place where the plant scientists are taken seriously by mainstream biomedical research."
Dangl no longer has trouble identifying a plant cell under a microscope. He is a recognized leader in the community of scientists studying plant–microbe interactions and an enthusiastic advocate for plant research. "Plants matter a lot," he says simply. "People in the developed world have sort of lost touch with how, every day, plants are part of their lives—from food, shelter, clothing, and fuel to the simple beauty of a garden." It is an exciting time in plant biology, he says, with big questions still to be answered and new tools to apply to those problems. He's hoping his appointment as an HHMI-GBMF investigator will help him recruit smart and creative young scientists to his lab to help him tackle some of those problems.
In a few months, Dangl will move his lab, which he shares with his wife, microbiologist Sarah Grant, to the university's new genome sciences center. The space will allow for more direct interaction between scientists working at the bench and computational biologists, which will be important as he begins to delve into a new research area. While the pathogen-defense research will continue, Dangl is expanding his view of plants' interactions with microbes: he now plans to examine how a plant and its genes influence the complete community of microbes—beneficial, pathogenic, and everything in between—that live in association with its roots.