Collaborative Research: Bottom-up Construction of a Synthetic Neuron and Programmable Neuronal Network

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Building synthetic cells is an exciting area of synthetic biology with opportunities to unravel basic design and organizational principles of cellular life. Dr. Liu and his collaborative team have identified the neuron as a potentially tractable cell to construct from the ground (bottom) up. Neurons convert biochemical signals to electrical dynamics and back to biochemical signals in animals. This project aims to construct a synthetic neuron with a modular design and a programmable synthetic neuronal network capable of recapitulating basic functions of a natural neuronal system. The team's design approach is to take inspiration from what is already known in the make-up of natural neurons, divide them into essential building blocks and construct each building block through the incorporation of proteins and materials, and assemble the established building blocks into functional subunits capable of performing part of neuron or neuronal network functionality. To investigate public perceptions of bottom-up synthetic biology and societal implications of the synthetic neuron, the project will convene deliberative group discussions. The research team is dedicated to breaking new ground in building synthetic cells, co-training the next generation of interdisciplinary scientists, and fostering an informed and participative public.This research combines experimental and modeling approaches and will address three broad goals of 1) reconstituting action potential and synapses in a single synthetic neuron; 2) engineering a synthetic multi-neuron system with defined network organization; and 3) broadening public benefits and ensuring inclusion in responsible research and innovation on the potentially high-benefit and high-risk synthetic neuron project. Enabled by advances in synthetic biology along with microfluidics, micromanipulation and engineering designs, synthetic neurons will be constructed by incorporating native ion channels and/or engineered proteins with defined molecular composition in vesicles with defined geometry. The collective knowledge generated through this endeavor will advance neuroscience through the elucidation of the minimal components to achieve neuronal functions and how neuronal morphology governs neuronal functions. By developing a de novo mechanism of synaptic communication using engineered proteins and aided with modeling, important new insights will be gained into the design principles of neuronal communication.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.