Plant biochemist Ryan Nett has joined MCB as an Assistant Professor. His lab will investigate how plants build small molecules, including compounds with medicinal potential. He is also interested in how these molecules shape plant biology and how they may affect other organisms that eat, infect, or coexist alongside plants.
“We’re really excited to have Ryan joining MCB,” says MCB Chair Sean Eddy. “Biochemistry is one of MCB’s historical strengths, and it’s an area that’s been going through something of a renaissance lately due to new tools and approaches. We think Ryan’s work on biosynthetic pathways for small molecules in plants is at the forefront of that renaissance.”
Ryan says that the diverse array of expertises in MCB will likely lead to many conversations and collaborations exploring these small molecules’ roles in plant metabolism and behavior. “These small molecules have likely evolved to influence organisms that interact with the plant (presumably by binding to a specific target), and plants have evolved really unique strategies to build these diverse, bioactive structures,” he says. “This is a major mechanism by which plants are able to interact and “communicate” with their environment, so I think studying these molecules will give unique insight into the mechanisms that plants use to survive in hostile environments where everything wants to eat them!”
Although his focus on biosynthetic pathways in plants didn’t emerge until grad school, science has always been part of Ryan’s life. He grew up in a small midwestern town in Illinois, where his father was a microbiology professor at the community college. As a kid, Ryan would often look at the pictures in science textbooks his dad brought home or read about the origins of the universe in books gifted by his grandfather. Outside of science, Ryan was involved in several sports growing up, including football, baseball, and basketball. His favorite sport was basketball, which he played competitively in high school and college and still plays recreationally. He hopes to connect with new neighbors and colleagues through basketball in Massachusetts.
As an undergraduate at Gustavus Adolphus College, Ryan’s favorite classes were ones that took students out into the field—such as entomology and aquatic biology—but he found chemistry and molecular interactions interesting as well. “I didn’t have a plan or anything like that; I just knew I was interested in studying the natural world,” Ryan says. Although he had initially considered becoming a premed, his experiences in class and conversations with his advisor convinced Ryan that he wanted to work on fundamental scientific questions in basic biology.
Ryan continued on to grad school at Iowa State University. One of his first year rotations was in Reuben J. Peters’s lab, which studies how plants produce diterpenoid natural products. Ryan had never been particularly focused on plants, but he enjoyed the scientific questions and the culture of the lab and opted to conduct his thesis research there.
Diterpenoids are a diverse class of biomolecules, and Ryan’s thesis work focused on gibberellins, a group of diterpenoids that serve as signaling molecules and hormones regulating processes like germination and shoot growth in many plants. However, gibberellins are also made by microbes that live in and around plants, including both pathogenic fungi and symbiotic bacteria that provide nitrogen to the plants. Ryan’s goal was to understand how and why beneficial bacteria would make these molecules, so he focused on gibberellin production in nitrogen-fixing bacteria that live in the root nodules of legumes, such as soybeans and common beans.
“At first glance, it wasn’t entirely clear why symbiotic bacteria would be producing a plant hormone that’s also produced by pathogens to trick the plant and infect the plant better,” Ryan says. “I would never say that it’s a resolved issue, but it seems like these hormones affect the development of the nodules that the bacteria reside in.” In the legumes he studied, the presence of gibberellin-producing microbes led the nodules to grow larger, providing more space for a larger number of bacteria, which gives an evolutionary advantage to the gibberellin-producing microbes.
During grad school, Ryan met the woman he would eventually marry, Bri, while co-teaching a biochemistry class. Through Bri, Ryan got into the art of mushroom hunting, a hobby that the couple still do together, sometimes with their 1-year-old son Fred. Ryan says that the family is looking forward to mushroom foraging in Massachusetts and that they’re hoping to find people to join them.
By the end of his Ph.D. work, Ryan was sure that he wanted to pursue a career in research and applied to join Elizabeth Sattely’s lab, which was publishing ambitious papers addressing the challenges of studying biosynthesis in plants. Compared to bacterial or animal genomes, plant genomes are very large and prone to chromosome duplications and rearrangements. Genes that form a pathway are often scattered across different chromosomes, making them harder for scientists to identify. Adding complication, many plants are slow-growing and difficult to cultivate. Some plants are harvested to the brink of extinction because of their medicinal properties, prompting scientists to look for ways to replicate molecule-building pathways.
“The Sattely Lab was pushing the envelope on how quickly we could uncover these pathways and think about engineering biosynthesis for medicinal compounds,” Ryan says. “It was just everything that I was interested in at that point in time.”
In Sattely’s lab, Ryan investigated a molecule called colchicine and its biosynthetic pathways in a lily plant called Gloriosa superba. Plants that contain colchicine have been used to treat inflammatory disease such as gout for hundreds of years. Ryan found an entire colchicine synthesis pathway in Gloriosa superba and transferred the colchicine pathway into a close relative of the tobacco plant, which is much easier to grow in a lab. This work demonstrated the ability to rapidly identify biosynthetic pathways in a medicinal plant and further established a proof-of-concept for engineering the production of a plant-derived drug in a model organism.
Now that he’s establishing his own lab at Harvard, Ryan says he may continue on a few research threads from earlier in his career but is also interested in addressing more complex questions related to plant metabolism. “I think there’s a lot to be learned about the entire chemical repertoire of these plants,” he says. “The fact that they’re making hundreds of different molecules means that there’s not only interesting enzymes and new chemistry to be found but also that plants produce this chemical diversity for a specific purpose, and I hope that my lab can help to further our understanding of this complexity”
In addition to enzyme biochemistry, Ryan’s lab will also be applying cutting-edge genetic and transcriptomic techniques to questions in plant metabolism, providing opportunities for undergraduates and graduate students to formulate and test their own hypotheses.
“It’s always great to give plant research a chance,” Ryan says. “For whatever reason, it’s not always at the forefront of people’s minds. At least, it wasn’t at the forefront of mine when I was in undergrad. But once you start studying plants, you find out there’s tons of interesting things happening in them–whether it’s their metabolism or in their growth and development or their genetics and genomics.”
He adds, “I’m excited to get my lab up and running and to have the chance to work with new trainees and scientists. To that end, I am hoping to recruit postdocs and a research technician, and I’m looking forward to bringing new grad students and undergrads into the lab. There are multiple projects that we will be investigating related to plant chemistry, including biochemistry of novel enzyme functionalities, characterization of specialized metabolism, and elucidation of small molecule mechanism of action, so I’m hopeful that this broad range of topics will attract some great people to the group!”