Unraveling the Mysteries of Metabolism

EAST LANSING, Mich. — Metabolism regulates far more than just body fat—it encompasses all the various life-sustaining chemical reactions that occur within an organism. When food is broken down into energy, a wide range of metabolites are produced. Primary metabolites help regulate and enable normal growth, while secondary metabolites provide unique advantages to an organism based on adaptations to their environment.

Despite the ubiquity and importance of metabolism, the processes underpinning it remain understudied, according to Seung Yon (Sue) Rhee, MSU Research Foundation Professor in the College of Natural Science and Director of the Plant Resilience Institute.

Rhee, who started at MSU on July 1, brings with her an idea of how to correct this, and a newly approved $3 million National Science Foundation grant to make it happen. Rhee says that the project’s goal is to “get more scientists involved in studying plant metabolism,” and how this complex system of reactions relates to other realms of plant biology.

The grant, awarded through the National Science Foundation’s Plant Genome Research Program, will help grow the Plant Metabolic Network, or PMN, a repository of essential genomic information aimed at connecting and accelerating worldwide research on plant metabolism. The plan is to expand the PMN from its current state—annotations of 126 species—to annotations of over 1000 species. Annotating genomes serves as a way to index the functions of sections of genetic code.

The PMN is a collection of databases that serves as a sort of online encyclopedia of the various metabolic pathways that occur within plants. If researchers discover that an organism produces certain compounds in response to a stressor, such as when a pest feeds on a plant, they could then use PMN to identify which of the plant’s genes are involved in producing that compound. By working to understand metabolism, scientists can identify how plants achieve important qualities like pest resistance, drought tolerance, and more.

As scientists begin to better understand an organism's component genetic characteristics, including the roles and characteristics of secondary metabolites, they can begin to improve efforts to genetically engineer more resilient plants. The team hopes that the PMN can connect the efforts of plant researchers worldwide to create a resource for understanding and engineering plant metabolism.

Rhee, who serves as the project’s principal investigator, explains that the team will “combine computational prediction with experimental testing.” The goal, she articulates, is to iteratively work to compile understanding, one annotation at a time.

Rhee describes the project as “a radical departure” from previous approaches to studying metabolism, and even to the original concept of the PMN itself. The project began as a computational experiment, focused on indexing information, but, as Rhee explains, “we’ve sort of stretched the limit of what we can accomplish with computational prediction.”

Zerbe, an associate professor in the UC Davis College of Biological Sciences, explains that the project’s importance stems from a discrepancy between how many plant genomes have been sequenced, and how well those genomes are understood. “While it has become cheap and easy to sequence the genomes of plants,” Zerbe explains, "there are still many cases where we don’t know what the genes we’ve sequenced actually do.”

Maeda, a professor in the UW-Madison Department of Botany, explains “my lab has established an experimental pipeline to obtain a large functional data set of one class of enzymes,” and that, “joining this new project will allow us to combine our growing number of experimental data with other enzyme functional data to generate and improve the community PMN database.” Maeda hopes that this project will, “advance our understanding and prediction of plant metabolic network functions.”

The Maeda and Zerbe labs will conduct assays of various plants to identify up to 200 enzymes important to plant metabolism. This data will then be fed to the PMN, establishing a lab-to-database pipeline that the team hopes will set a precedent for future collaborators.

Zerbe hopes that the creation of an accessible, collaborative tool will help disrupt the "one-lab-one-enzyme" model under which many plant researchers operate. He hopes that this project aids in the creation of a "consortium community" that can “feed data straight into databases,” expediting research as a result.

The grant includes components to improve the usability of PMN as well. These include improvements to the PMN’s interface and plans to host seminars at conferences. These seminars will provide training to researchers on how to contribute to—and source information from—the network, while also attempting to increase the number of users using the PMN.

The project also includes educational programs to help foster students’ curiosity and interest in plant science, particularly among groups that are traditionally underrepresented in the field. Rhee sees these initiatives as a chance to foster an interest in STEM among a diverse group.

The Zerbe lab will facilitate CURE courses at UC Davis, where undergraduate students will have the opportunity to engage with modern methods in biochemical plant research. Outreach activities are also planned for students in secondary education. The grant includes provisions for creating educational videos, podcasts, tutorials, and other multimedia projects to help foster students’ excitement about studying plant metabolism.