Carnegie Science | Spring 2019 19 Medicinal plants and plant-derived compounds have been in humanity’s medicine chest for millennia to treat ailments from wound healing to neurological disorders. Some 80% of humanity relies on herbal medicine. Now scientists from Carnegie and Stanford University will use the tiny laboratory worm C. elegans, which has some 75% genetic similarity to humans, to identify which plant molecules are at work and how they affect the brain’s biochemistry. The project, called NeuroPlant, could lead to new ways to develop drugs to treat neurological and psychiatric diseases. The Wu Tsai Neurosciences Institute is funding this work with a “Big Ideas” grant that supports “cross-disciplinary teams transforming our understanding of the brain.” “We’re interested in finding out what the mode of action is of these compounds from plants that have known effects on the human nervous system,” said Carnegie’s Sue Rhee, one of NeuroPlant’s principal investigators. “I think it’s an interesting place where we can potentially connect things like ethnobotany and plant science with neuroscience and perhaps even medicine.” The central foundation for the NeuroPlant project is the fact that plants have a powerful impact on our behavior and health, from the use of herbal medicine to modern drugs, including neurological drugs. Rhee wondered which plant molecules affect our behavior and health and what they are doing to us. In a conversation with Stanford professor of molecular and cellular physiology Miriam Goodman, Rhee learned that the tiny roundworm C. elegans, could be the perfect model organism for pursuing these questions. It allows the NeuroPlant team to study behavior, nervous systems, and genetics at the same time. The combination of Rhee’s expertise in plant science, Goodman’s knowledge of the worm’s sensory systems, and Stanford’s Thomas Clandinin’s expertise in neurobiology and genetics, the team believed that they could develop a new method for unraveling the neurological effects of plant-derived compounds. The first plant the team will study is valerian. It has been used for millennia for treating mild anxiety, and it is used in epilepsy drugs. The team will observe how the worms respond. If the techniques prove successful, they will experiment with other plants used in neurologic medicines. The team wants to understand the genetic and neural pathways the extract uses, and they hope to discover new drugs. Currently, Goodman said, most drugs are developed by screening one molecule at a time and focusing on one genetic pathway. If the NeuroPlant method works, researchers could screen numerous possible drugs at once, and how they affect multiple genetic pathways, which could potentially speed the identification of new treatments. “I’m not expecting those chemicals to be drugs that could actually treat disease,” Goodman said. “But if we can identify targets, if we can identify chemicals, it becomes a productive entry point for a new way to develop new drugs.”  “ . . . the team believed that they could develop a new method for unraveling the neurological effects of plant-derived compounds.” Worms to Shed Light on Neurological Effects of Plant Compounds The tiny roundworm C. elegans, about one millimeter long, is a useful model organism for studying many aspects of genetics and development. Some 75% of the worm’s genes have equivalent genes in humans. Carnegie’s Sue Rhee (left) with Stanford’s Thomas Clandinin (middle) and Miriam B. Goodman (right) discuss the NeuroPlant project. Image courtesy L.A. Cicero The NeuroPlant researchers will first study how extracts from the valerian plant affect the worm C. elegans. Valerian’s therapeutic powers have been used since early Greece to treat nervousness, heart palpitations, and more. It is used today for insomnia and anxiety, among other conditions. Image courtesy Creative Commons