A botanical armamentarium
​for neurological therapeutics.  

Twenty percent of American adults have experienced a mental health issue. Yet, despite decades of research we still have a limited understanding of how the mind works. NeuroPlant aims to address this gap by leveraging chemicals made in plants as tools to manipulate and decipher neuronal pathways.

Plants have evolved extraordinarily complex chemistry to fight predators and parasites. These metabolic pathways produce a plethora of chemicals with the potential for therapeutic use in humans. Chance exploration of plant extracts has led to some of the most powerful, selective chemical actuators of brain function, including morphine, cannabinoids, nicotine, and cocaine. Systematic screening campaigns have produced >3,000 plants with anticancer activity, and many clinical agents including taxol, topotecan, and CPT-11. We aim to remove existing barriers that prevent exploration of these molecules for research and therapeutic benefits.

Our Strategy

Our strategy is to develop methods to screen the effects of natural products on neural activity and behavior. We will focus on compounds synthesized by medicinal plants, as these chemical libraries are enriched for their efficacy through evolution and human selection. Our principal experimental system is the roundworm C. elegans, which is uniquely suited for this project due to its rapid growth, its genetic and optical accessibility, and its wealth of genomic resources. After screening in worms, we will test our lead compounds in human cells. ​

Our Screens

---

In Phase 1, we achieved three high-level goals:
1) developed an efficient phenotyping platform enabling exhaustive characterization of chemotaxis behavior,
2) combined genetic dissection with this platform to identify plant secondary metabolites
that evoke this behavior and pair them with molecular targets,
3) discovered how ethologically relevant chemical cues are encoded in the nematode nervous system, exploiting the relative simplicity of this animal to provide the first comprehensive view of how context-appropriate behaviors can emerge from a complex sensory milieu.

In Phase 2, we will expand our efforts to:
1) optimize and apply high-content behavioral screens to discover novel chemical
actuators of the nervous system,
2) discover novel ligand-receptor pairs in nematodes and humans,
3) define neural codes underpinning chemosensory valence.

​Through the discovery of a rich repertoire of chemical actuators and their molecular targets in invertebrates and humans, this work will define entry points from which novel therapeutics can be derived and illuminate how ethologically relevant stimuli are decoded by the brain. Understanding the chemico-informatic and neural logic responsible for a directed behavior like chemotaxis at the level of cells, circuits and biophysically realized models will set an important paradigmatic example for systems neuroscience.

In a parallel project, we will blend understudied plant-derived compounds and potential membrane receptors together with an efficient pipeline for linking compounds to nociception and to receptors that are conserved members of the druggable human genome. As more than 80% of these membrane proteins are conserved in C. elegans and this model organism is a proven platform for phenotypic screens, we propose screens for compounds and genes affecting nociception as well as to identify novel ligand-receptor pairs using C. elegans. We will:
1) determine how putative analgesics made by plants affect nociceptive
2) link membrane receptors to plant-derived neuroactive compounds.

This innovative research project has the potential to determine the function of the specified genes in nociception and to reveal novel ligand-receptor pairs that could serve as new entry points for improved or alternative pain treatments.