Using plants as a model, studying “the complexity and reproducibility” of developmental biology

Almost paper-thin, often with a complex two-dimensional shape, the leaves can number in the hundreds of thousands on an organism like a white oak tree. Yet, generally, each leaf appears quite similar in shape.

How is it that a plant coordinates the production of these leaves, one after another, so carefully and so repeatably?

The molecular forces governing this aspect of plant development are the focus of Aman Husbands, who joined the faculty of Penn’s biology department in the School of Arts and Sciences in January. By exploring proteins and protein families involved in different facets of plant growth, Husbands identified key regulators that seem fundamental to biology, and not just plant biology.

His curiosity-driven research not only sheds light on the basic mechanisms responsible for plant growth, but also has the potential to impact how plants remain resilient in the face of climate change. It may even shed light on aspects of development and disease in other species, including humans.

“You can break down the lab into complexity and reproducibility,” says Husbands, Presidential Assistant Professor of Biology Mitchell J. Blutt and Margo Krody Blutt. “How do you create these beautiful, intricate shapes? Biology should be wrong all the time, and yet it is not. We are interested in the responsible mechanisms.

Attracted to plants

As a child, Husbands, who grew up in Toronto, “wanted to be a marine biologist, like everyone else,” he says. Around his second year at the University of Toronto, as he began to take more specialized science courses, another aspect of biology caught his attention.

“Plants, for some reason, I loved,” he says. “It was a system that I understood intuitively.”

Plant leaves begin to form as a small bump and then flatten into a complex two-dimensional shape. Some of Husbands’ research examines how plants consistently form “those paper-thin structures over and over again,” rarely getting it wrong.

During his undergraduate years, he worked with Nancy Dengler, whose lab group studies plant anatomy. Anatomy was also a focus of the lab he joined for his graduate studies at the University of California, Riverside. But after six months, he joined the lab of Patricia Springer, who “was asking really interesting questions about plant development, including how plants establish boundaries between their organs,” says Husbands. Springer gave him the freedom to explore the molecular aspects of plant development, and he began to ask questions about protein function.

His doctoral research focused on a family known as the LOB DOMAIN (LBD) genes, transcription factors that control how and when genes are turned on and off. “People assumed they were transcription factors, but that hadn’t been formally demonstrated,” he says. Under Harley Smith, another Riverside faculty member at the time, Husbands acquired the molecular biology skills to pursue these questions, identifying the binding site recognized by this family of proteins, which is specific to plants. “I’m still proud of this newspaper,” he says.

Returning to the East Coast for his postdoctoral work, he joined the laboratory of Marja Timmermans at Cold Spring Harbor Laboratory in New York. Together with Timmermans, now at Germany’s University of Tübingen, Husbands began to delve into a complex of transcription factors that still constitutes the “bread and butter” of his research today, known as HD-ZIPIII. . “What interested me about this family is that it’s very, very deeply conserved,” he says, with its origins dating back 750 million years or more in evolutionary time. HD-ZIPIII genes, if manipulated, impact multiple aspects of plant development, Husbands says, including stem cells, the plant vein system, and leaf architecture.

When Leaf Formation Goes Wrong

As Husbands left Cold Spring Harbor to take up a professorship at Ohio State University, where he ran a lab for four years, and now at Penn, one question that drives his work is: how can plants reliably produce sheets that look like they’re supposed to look? The term used by plant biologists for this is reproducibility or hardiness, and Husbands studies it in the context of flat-leaf architecture, or the tendency for plants to constantly form “those paper-thin structures over and over again. “, he says. “What makes this more compelling is that the sheets don’t start out flat.” When they initially expand, they are ball-shaped and only later flatten into what most would recognize as a leaf: a thin shape with a distinctive two-dimensional shape.

“It’s a very difficult process,” says Husbands. Plants generally do well, but leaf growth sometimes goes wrong. “You might have leaves curling up or down, which will impact fitness,” he says.

As a general rule, however, says Husbands, “the sheets always know, ‘That’s my top; it’s my ass. I have a limit from which to grow.

The concept of limits that stimulate growth is not unique to plants, but is present in almost all developing organisms. So the ideas that Husbands pulls from the factories can also have applications in other bands. “It’s a very classic development paradigm,” he says.

Other Husbands projects involve collaborations with computational biologists and mathematicians. In one, he and his colleagues hope to search for patterns in gene expression data in the hope that new candidate genes will emerge as central to the reproducibility and robustness of flat-leaf architecture.

Applications, partnerships and inspiration

While Husbands is driven by a love of basic science and discovery, he also steers his work in directions that may one day find real-world application. On the plant side, he notes that “robustness engineering”, by intervening with some of the transcription factors he studies, could allow plants to resist the vagaries of climate change. “We’re a long way from that, but if you could find a particular system that’s sensitive to climate change, you could use those properties to shore it up, stabilize that biology, and make the plant resilient to climate change. climatic extremes.

Three scientists in a lab monitor some experiments, while a fourth works in the background.

Husbands and lab members Sarah Choudury, Nicole Callery and Courtney Dresden are collaborating to explore the molecular players involved in how plants regulate leaf development.

Beyond plants, Husbands and his interns are also studying how the lipid-binding domains they studied in plants function in proteins found in the tree of life, including a tumor suppressor protein found in plants. ‘male. “We want to leverage insights from our work and others to develop strategies to affect the activity of this tumor suppressor via this lipid-binding domain,” he says. “The therapeutic applications are obvious. If you’re developing a ligand to affect the activity of a tumor suppressor, you’re in business.

With a strong department in plant biology as well as many other facets of science, and additional potential collaborators just around the corner on campus, Husbands jumped at the chance to come to Penn. “Penn is Penn,” he said. “During the recruiting process, just reading what everyone was doing and their science, it’s just a fire hose. You walk away and get inspired.

Biologist Aman Husbands in his lab

Sharon D. Cole