Profile of Deborah P. Delmer

For small-scale African farmers, “we are trying strategies to optimize yield under conditions of stress and low inputs.”

In 2001, Deborah P. Delmer, then chair of the Section of Plant Biology at the University of California, Davis (Davis, CA), reached a crossroads in her life. She had already amassed a long and distinguished research career in plant biology, having been one of the first to uncover the enzymes and biochemical mechanisms for tryptophan synthesis, protein glycosylation, sucrose degradation, and, most importantly, cellulose biosynthesis. Although questions about the biochemistry of plant cells constantly remained, Delmer was ready for something different.

“At that point, my husband had passed away and my daughter, who had grown up mostly in Israel and didn't particularly like Davis, had gone back to Jerusalem to finish high school and go to the Israeli army,” she recalls. “So I was on my own and I began thinking, `Life is short, and I need one more challenge in my life.'” She then remembered something that her father, Thomas Pierson, who had been a physician in rural Indiana, had told her about medicine: “He said, `What's great about medicine is that you can do science, which is fascinating, but you can also help people.' And you know what, I really would like to do some good in the world, but what could I do as a plant biologist?”

Delmer then discovered that The Rockefeller Foundation, a global philanthropic group based in New York, was looking for someone who had broad experience in plant biochemistry and molecular biology. “They wanted someone to help them make decisions on how the new, high-end plant science would be relevant to their grant-making in support of programs aimed at crop improvement,” she says. Delmer felt drawn to this opening, and in January 2002, she closed her own laboratory and accepted the position as The Rockefeller Foundation's Associate Director for Food Security.

In her Inaugural Article in this issue of PNAS (1), Delmer, elected to the National Academy of Sciences in 2004, discusses some of the main issues and strategies involved in agricultural development in Africa, which has been the focus of her work for The Rockefeller Foundation. “If you look at the models for genetically modified crops, for example, they're based on farmers in Iowa not farmers in Africa, who have completely different problems,” she says. “How can we try to make a connection between the genomics revolution and these new innovations in plant science and a farmer in Uganda?” Of course, there are no easy answers, she points out: “You have to deal with so many complex issues, and that's what makes it fascinating and frustrating at the same time.”

Auspicious Beginnings

Delmer was born in Indianapolis, IN, in 1941 and raised in the nearby farming community of New Palestine, IN. Her father was a major influence in her life, providing a nourishing environment while she was growing up. “He treated me differently from many girls in small Midwestern towns who were taught they would be suitable to be secretaries,” she says. “Every time I wanted to be a stewardess, he told me, `No, you want to be an airline pilot.'”

Delmer's father wanted her to follow in his footsteps. “He was a people person,” she says. “He loved his work and was passionate about it, and he wanted me to be a doctor as well.” Although Delmer became interested in science, she chose to venture into microbiology instead of medicine after she enrolled at Indiana University (Bloomington, IN) in 1959. The decision, she admits, disappointed her father. At Indiana University, Delmer also became interested in biochemistry after taking a class with Walter Konetzka. “He was an unbelievable lecturer,” she recalls. “He could make boring things so fun and exciting, and I got a passion for biochemistry from this guy.”

After graduating from Indiana University with departmental honors, Delmer chose to try something a little different in graduate school. In 1963, she traveled west to the Scripps Institute of Oceanography (San Diego, CA) to pursue a degree in marine microbiology. “It sounded very exotic, and it would get me out of Indiana and into some adventure,” she says. It turned out to be a little too adventurous, though, as Delmer became seasick on her first voyage out to sea: “I then decided that this wasn't for me and quickly switched over to the new biology department at U.C. San Diego.”

At the University of California, San Diego (UCSD, La Jolla, CA), Delmer began studying plant biology almost by accident. Carlos Miller, an Indiana University plant scientist, happened to be at UCSD on sabbatical during that time, and Delmer was given a rotation with Miller to learn about plant tissue culture and tryptophan synthesis. “Everybody in that department worked on tryptophan, but nobody had ever looked at it in plants,” she says. “So we asked, `How do plants make tryptophan?' I got to doing my thesis on that project, knowing nothing about plants at the beginning, but then I started to become a plant biochemist, I guess.” By the time Delmer graduated, she had transitioned to plant biochemistry quite well, and she successfully elucidated the pathway for tryptophan biosynthesis in plants (2, 3).

A Scientific Vagabond

After receiving her Ph.D. in cellular biology at UCSD in 1968, Delmer began what would become a peripatetic research career. Her first stop was at the University of Colorado (Boulder, CO), where she followed her then-husband, an astrophysicist whom she had met at UCSD. Delmer found a rewarding postdoctoral opportunity in Boulder with Peter Albersheim, a young professor who would later become a pioneer of plant cell structure. “That's where I got started on studying the plant cell wall,” she says, “although with Peter, I worked on the enzyme sucrose synthase.” Delmer was one of the first investigators to purify sucrose synthase to completion and to study its role in sucrose synthesis and degradation (4).

After bouncing back to UCSD for a postdoctoral stint in Stan Mills's laboratory, Delmer's career began to flourish with her first faculty job in 1974 at Michigan State University's Plant Research Laboratory (East Lansing, MI). Here, she took up what would become her life's main research interest: how plants synthesize cellulose for their cell walls. “It's the world's most abundant organic compound, but nobody had a clue how plants made it,” Delmer says.

Having already elucidated the synthesis of tryptophan, she embarked on this new research challenge and used a biochemical approach to try to uncover the pathway that results in the polymerization of glucose molecules into the glucan chains that comprise cellulose. “We knew this [process] had to be a membrane-bound activity, and we suspected the substrate was UDP-glucose,” she says, “so we started looking for some plasma membrane enzyme that would polymerize these glucans. I took up the cotton fiber as a model system because cotton fibers are these wonderful single cells that at the end of their life, they end up being 90% cellulose, so they're really little cellulose factories.”

Unfortunately, Delmer's biochemical approach turned out to be unfruitful. Despite multiple efforts to make cellulose outside of the cells, she and postdoctoral researcher Ursula Heiniger repeatedly ended up with the same two products: a sterylglucoside and callose, a β-1,3 glucan polymer (5, 6). Cellulose is a β-1,4 glucan polymer. “As time went on, we continued our pursuit almost alone,” she says. “There were very few people left trying to synthesize [cellulose] because nobody could get anywhere. It wasn't until later, when we were finally able to identify and clone the genes, that we started making real progress.”

“But the kinds of things we did do while at Michigan State were still valuable,” she adds. From the work of postdoctoral researcher Mary Ericson, Delmer's laboratory was the first to show that plants, like animals, used a lipid intermediate in the process of protein glycosylation (7, 8). Graduate student Maureen Meinert carried out initial studies on the structure and development of cotton fiber cell walls (9), and a group led by postdoctoral researcher Nick Carpita performed some of the first measurements of the porosity of plant cell walls (10). Overall, Delmer says she had a fantastic experience while at the Plant Research Laboratory, surrounded by supportive colleagues and plenty of funding opportunities, especially from the Department of Energy (DOE): “That was a Department of Energy lab, and I think the long-standing support from the DOE for my research has made all the difference in my life.”

New Approaches to Old Questions

In 1974, Delmer met a fellow researcher who would help change the course of her career. The head of the Volcani Institute in Israel, Yoash Vaadia, came to the Plant Research Laboratory as a visiting professor. “[Vaadia] had a great interest in developing world agriculture and applied aspects of agriculture that certainly influenced my later career decisions,” says Delmer. She and Vaadia developed a deep personal relationship, resulting in her move to and acceptance of a faculty position at The Hebrew University of Jerusalem in 1987.

While in Israel, Delmer's laboratory made one of its most unusual discoveries. Postdoctoral researcher Estie Shedletzky “was looking at inhibitors of cellulose synthesis, and along the way we created some cell cultures that became resistant to the inhibitors,” says Delmer. “The odd way in which these cells adapted was to learn to live with no cellulose in their wall. It turns out these walls were much weaker than normal, because the main load-bearing network in cell walls is an interaction between cellulose and xyloglucan. While these crazy cells still produced xyloglucan, they just spit it out into the media and ended up with cell walls that were almost exclusively pectin” (11). Delmer notes that these cells provided valuable insight into the relationship between cellulose and other cell wall polymers.

In collaboration with Candace Haigler, Delmer also returned to another old research interest, sucrose synthase. With graduate student Meme Amor, Delmer and Haigler showed that a membrane-bound form of sucrose synthase plays a key role in channeling UDP-glucose to the cellulose synthase complex (12).

Delmer also had continued her quest to pinpoint the enzymes responsible for cellulose synthesis. Delmer applied advances in molecular biology and genetics to change her investigative approach, but the results were unfortunately the same. “We had tried to just use sequences from bacterial genes to pick up genes for cellulose synthesis in plants, and we never had success in doing that,” she says. A breakthrough occurred, however, with the help of David Stalker, a researcher at Calgene Inc. (Davis, CA) who also was interested in cellulose and cotton fiber. “He was trying to find promoters that were highly active in the fiber,” say Delmer, “and we were looking for the cellulose synthesis genes that should also be highly expressed in the fiber.” In 1993, Amor harvested RNA from cotton fibers during the stage where cellulose synthesis approached its maximum rate and prepared a cDNA library that was sent to Stalker and his colleagues. “We just started looking at random sequences, and we quickly came across something that looked as if it could be the catalytic subunit for cellulose synthesis,” she says. Delmer and her group found two cDNA clones sharing homology with CelA, the bacterial gene that catalyzes the synthesis of cellulose and is highly expressed in the fiber. The study also revealed that plant cellulose synthase genes have several domains that are unique to plants and not found in their bacterial counterparts (13).

“I think that was a seminal contribution, in terms of molecular biology, to cellulose synthesis,” says Delmer. “It was the first identification of any plant gene involved in this process.” Delmer thinks that this initial discovery revitalized the field of cellulose biosynthesis. “All of the young and avid people suddenly got interested,” she says. Soon, several other related genes in this family, CesA, were revealed, which allowed researchers to begin doing mutational studies on the proteins to examine the mechanisms of action. “I think a whole new community has evolved now to work on this process, and it's really opened up the whole field,” says Delmer.

Delmer and Vaadia returned to the United States in 1997, and Delmer took over as chair of the University of California, Davis, Section of Plant Biology, where she would spend 5 years before leaving research. Fittingly, one of her last experiments managed to answer one of her first research questions, namely why sterylglucoside appeared as an end product in her attempts at synthesizing cellulose. “We had just assumed it was a random lipid product synthesized from UDP-glucose and had no relationship to cellulose synthesis,” she says. But with postdoctoral researcher Liangcai Peng, Delmer found that although the CesA enzymes can add new glucose molecules onto an existing cellulose chain, the enzymes cannot begin a chain from scratch. The sterylglucoside was found to serve as a primer to initiate cellulose synthesis (14).

From Bench to Field

In 2002, Delmer made the major transition of leaving the laboratory bench to enter the fields of Africa for The Rockefeller Foundation. In her PNAS Inaugural Article (1), she discusses the need for plant biologists to devote more energy to the realm of translational science, much like the health sciences have recently done. For whereas basic scientists are making remarkable strides in understanding fundamental processes involved in plant growth and development, the global rate of crop production is on the decline, especially in the poorest global regions, such as sub-Saharan Africa.

Delmer particularly highlights abiotic stresses, such as poor soil quality, metal toxicity, and drought, and biotic stresses such as pests, pathogens, and parasitic organisms, as two central problems facing African farmers. “Small-scale farmers in Africa are working under conditions of extremely low inputs, and they can't afford expensive inputs such as irrigation, fertilizers, and pesticides,” she explains. “So we are not focusing on maximizing yield potential, such as we did previously in Asia with the rice fields. Instead we are trying strategies to optimize yield under conditions of stress and low inputs.”

With extensive sequence information, genetic maps, and molecular markers existing for many crops, molecular breeding could be one tool to provide these farmers with crop strains best suited for their environment, suggests Delmer. “We could build tolerance to drought, to pests, and diseases directly into the seed,” she says. Some of the current genetically modified crops developed by the private sector are beginning to prove valuable to small-scale farmers, but Delmer points out that a major challenge for the public sector will be to use the new technologies to develop valuable traits in those crops that are not of interest to the private sector yet are extremely important to poor farmers in the developing world.

The biggest impact may not be counted in fertilizer or seeds, however. “My boss Gary Toenniessen once told me, `The best thing we did in Asia was not so much the projects we supported, but the lasting legacy we left of having trained hundreds of Ph.D. scientists,'” says Delmer. “So human capacity building is a huge part of what we're trying to do in Africa, but it's going to require a sustained effort over a long time period.”

As for possibly resuming her own research work, Delmer is content at her current post. “Sometimes I miss the research and the rough-and-tumble camaraderie found in university life,” she says. “I also feel particularly proud to have mentored numerous individuals who have gone on to become recognized scientists in their own right.” But through her current work with the foundation, Delmer says, “I have come to have immense respect for the innate wisdom and resilience of poor farmers who face innumerable challenges on a daily basis. The chance to use science to enhance their livelihoods is indeed a rewarding opportunity. Leaving academia was a surprising turn of events in my life, but one I have never regretted.”