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Ullas Pedmale

From left, Daniele Rosado and Ullas Pedmale examine a sample of the model plant Arabidopsis. Photo courtesy of Ullas Pedmale

By Daniel Dunaief

Many plants are in an arms race akin to the developers of skyscrapers eager to get the most light for their prized penthouse apartments. Only, instead of trying to collect rent from well-heeled humans, these plants are trying to get the most sun, from which they create energy through photosynthesis.

Plants are so eager to get to the coveted sunlight that the part growing towards the light sends a distress signal to the roots when they are in the shade. While that might help an individual plant in the short term, it can create such shallow and ineffective roots that the plant becomes vulnerable to unfavorable weather. They also can’t get as many nutrients and water from the ground.

This is problematic for farmers, who want plants that grow in the sun, but that don’t sacrifice the development of their roots in the shade. Ullas Pedmale, Assistant Professor at Cold Spring Harbor Laboratory, is working to lend a hand.

Pedmale, who recently published research in the journal Plant Physiology, is studying the signals the shoots, or the parts of the plants either in the sunlight or the shade, send to the roots.

Pedmale and postdoctoral researcher Daniele Rosado, who is the first author on the recent paper, explored the genes that turned on in the roots of the model plant Arabidopsis and tomato plants when these plants were in the shade.

When plants are in the shade, they “prioritize shoot growth and try to outcompete the neighboring plants,” said Rosado. “That’s when root development is compromised.”

Among the genes that are active when plants are in the shade is a family of genes called WRKYs, which affect gene expression and cause stunted growth in the roots.

WRKY genes respond to stress. Keeping WRKY genes on all the time, even when a plant is in the sun, caused stunted growth of the roots. WRKY proteins turn on or off other genes.

This can be problematic for farmers, who tend to try to increase yield by putting more plants in an area. At that point, the plants shade each other, which is “bad for the root system. If we can find a way to get the roots to grow normally, we can potentially increase yield,” Rosado said.

This could also remove more carbon dioxide from the air and store it in the developing roots, helping to mitigate the effect of global warming. “Our study can give a roadmap on how to make longer, deeper roots,” Pedmale said.

At this point, researchers still don’t know how the plant transfers information about the amount of sunlight it receives in the green chloroplasts where photosynthesis occurs to the WRKY genes, which are in the nucleus.

Researchers have been studying the shade response in the shoots of plants for over five decades. They have not, however, focused as much attention on the effect of less sunlight on the roots.

“We want to tackle this problem,” Pedmale said.

WRKY genes are a generalized stress signal, which is not just involved when a plant isn’t getting enough light. They are also turned on during pathogen attacks, stress and amid developmental signals.

Indeed, plants in the shade that have turned on these signals are especially vulnerable to attacks. Caterpillars, for example, can eat most of a shaded plant because the plant is so focused on growing its shoot that its defenses are down.

When that same plant is in the sunlight, it is more effective at defending itself against caterpillars.

At this point, Pedmale doesn’t know whether these genes and signals occur across a broad species of plants beyond tomatoes and Arabidopsis. He and others are hoping to look for these genes in grasses and grains.

Pedmale is also searching for other signals between the shoot and the root. “Plants are masters of adaptation,” he said. “They might have redundant systems” that signal for roots to slow their growth while the shoots tap into the available energy to grow.

Plants may also have natural molecules that serve as brakes for the WRKY signal, preventing the shoot from taking all the available energy and rendering the plant structurally fragile.

A scientist at CSHL for five years, Pedmale came to the lab because of the talent of his colleagues, the reputation and opportunity at CSHL and the location.

Born and raised in Bangalore, India, Pedmale enjoys reading fiction and autobiographies and wood working when he’s not in the lab. He recently made a book shelf, which provides him with a chance to “switch off” from science, which, he said, is a 24-hour job. He has taken wood pieces from his workshop and brought them to PhD classes at CSHL, where he can show them plant biology and genetics at work.

Pedmale and his wife Priya Sridevi, who also works at CSHL, have a mini golden doodle named Henry.

A native of São Paulo, Brazil, Rosado is married to plant biologist Paula Elbl, who is the co-founder of a start up called GALY, which is trying to produce cotton in a lab instead of in a field.

Rosado is the first in her family to attend a public university. She has been working in Pedmale’s lab for two years and plans to continue her research on Long Island for at least another year.

Rosado knew Pedmale had worked as a post doctoral researcher in the lab of celebrated plant biologist Joanne Chory at the Salk Institute for Biological Studies. She met Pedmale at a plant conference, where she expressed an interest in his research.

Longer term, Rosado hopes her research has a broader impact.

“If I’m lucky, I’ll be able to see the fruits of my work being applied to make a difference and help feed people,” she said.

As for his work, Pedmale is eager to understand and use the signals from one part of a plant to another, given that the plant lacks a nervous system. “Once we can understand their language,” he said, “we can manipulate it to increase yield.”

Priya Sridevi with her golden doodle Henry. Photo by Ullas Pedmale

By Daniel Dunaief

Priya Sridevi started out working with plants but has since branched out to study human cancer. Indeed, the research investigator in Cold Spring Harbor Laboratory Cancer Center Director David Tuveson’s lab recently became the project manager for an ambitious effort coordinating cancer research among labs in three countries.

The National Cancer Institute is funding the creation of a Cancer Model Development Center, which supports the establishment of cancer models for pancreatic, breast, colorectal, lung, liver and other upper-gastrointestinal cancers. The models will be available to other interested researchers. Tuveson is leading the collaboration and CSHL Research Director David Spector is a co-principal investigator.

The team plans to create a biobank of organoids, which are three-dimensional models derived from human cancers and which mirror the genetic and cellular characteristics of tumors. Over the next 18 months, labs in Italy, the Netherlands and the United States, at Cold Spring Harbor Laboratory, expect to produce up to 150 organoid models.

The project officially started in January and the labs have been setting up the process through June. Sridevi is working with Hans Clevers of the Hubrecht Institute, who pioneered the development of organoids, and with Vincenzo Corbo and Aldo Scarpa at the University and Hospital Trust of Verona.

Sridevi’s former doctoral advisor Stephen Alexander, a professor of biological sciences at the University of Missouri, said Sridevi has had responsibilities beyond her own research. She was in charge of day-to-day operations in his lab, like ordering and regulatory reporting on radioactive material storage and usage, while he and his wife Hannah Alexander, who was Sridevi’s co-advisor, were on sabbatical. “She is hard working and determined,” said Alexander. “She knows how to get things done.”

In total, the project will likely include 25 people in the three centers. CSHL will hire an additional two or three scientists, including a postdoctoral researcher and a technician, while the Italian and Netherlands groups will also likely add another few scientists to each of their groups.

Each lab will be responsible for specific organoids. Tuveson’s lab, which has done considerable work in creating pancreatic cancer organoids, will create colorectal tumors and a few pancreatic cancer models, while Spector’s lab will create breast cancer organoids.

Clevers’ lab, meanwhile, will be responsible for creating breast and colorectal organoids, and the Italian team will create pancreatic cancer organoids. In addition, each of the teams will try to create organoids for other model systems, in areas like lung, cholangiocarcinomas, stomach cancer, neuroendocrine tumors and other cancers of the gastrointestinal tract.

For those additional cancers, there are no standard operating procedures, so technicians will need to develop new procedures to generate these models, Sridevi said. “We’ll be learning so much more” through those processes, Sridevi added. They might also learn about the dependencies of these cancers during the process of culturing them.

Sridevi was particularly grateful to the patients who donated their cells to these efforts. These patients are making significant contributions to medical research even though they, themselves, likely won’t benefit from these efforts, she said. In the United States, the patient samples will come from Northwell Health and the Tissue Donation Program of Northwell’s Feinstein Institute of Medical Research. “It’s remarkable that so many people are willing to do this,” Sridevi said. “Without them, there is no cancer model.”

Sridevi also appreciates the support of the philanthropists and foundations that provide funds to back these projects. Sridevi came to Tuveson’s lab last year, when she was seeking opportunities to contribute to translational efforts to help patients. She was involved in making drought and salinity resistant rice and transgenic tomato plants in her native India before earning her doctorate at the University of Missouri in Columbia.

Alexander recalled how Sridevi, who was recruited to join another department at the University of Missouri, showed up in his office unannounced and said she wanted to work in his lab. He said his lab was full and that she would have to be a teaching assistant to earn a stipend. He also suggested this wasn’t the optimal way to conduct research for a doctorate in molecular biology, which is a labor-intensive effort. “She was intelligent and determined,” Alexander marveled, adding that she was a teaching assistant seven times and obtained a wealth of knowledge about cell biology.

Sridevi, who lives on campus at CSHL with her husband Ullas Pedmale, an assistant professor at CSHL who studies the mechanisms involved in the response of plants to the environment, said the transition to Long Island was initially difficult after living for six years in San Diego.

“The weather spoiled us,” she said, although they and their goldendoodle Henry have become accustomed to life on Long Island. She appreciates the “wonderful colleagues” she works with who have made the couple feel welcome.

Sridevi believes the efforts she is involved with will play a role in understanding the biology of cancer and therapeutic opportunities researchers can pursue, which is one of the reasons she shifted her attention from plants. In Tuveson’s lab, she said she “feels more closely connected to patients” and is more “directly impacting their therapy.” She said the lab members don’t get to know the patients, but they hope to be involved in designing personalized therapy for them. In the Cancer Model Development Center, the scientists won a subcontract from Leidos Biomedical Research. If the study progresses as the scientists believe it should, it can be extended for another 18 months.

As for her work, Sridevi doesn’t look back on her decision to shift from plants to people. While she enjoyed her initial studies, she said she is “glad she made this transition” to modeling and understanding cancer.