NeuroPlant
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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

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In Phase 1, we will design three screening strategies:
1) imaging the activity of chemosensory neurons in worms 
2) identifying genes involved in attraction and repulsion in worms, as a functional measure of compound activity
3) performing high-throughput studies of engineering human G-protein-coupled receptors (GPCRs) in mammalian cells
​We envision that these innovative, scalable platforms will allow researchers to mine a plethora of small molecules. Our work will serve as an initial framework for studying combinatorial chemical logic with combinatorial neuronal circuit logic. 

Our Future

​In Phase 2 of this project, we will be well positioned to scale up and delineate the endogenous agonists of orphan GPCRs and the molecular pathways underlying chemosensation.
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