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

构建合成细胞是合成生物学的一个令人兴奋的领域，有机会揭示细胞生命的基本设计和组织原则。刘博士和他的合作团队已经确定神经元是一种潜在的可处理的细胞，可以从地面（底部）向上构建。在动物体内，神经元将生化信号转化为电动力学，再转化为生化信号。本项目旨在构建具有模块化设计的合成神经元和可编程的合成神经元网络，能够概括自然神经元系统的基本功能。该团队的设计方法是从已知的自然神经元组成中获得灵感，将它们划分为基本的构建块，并通过结合蛋白质和材料构建每个构建块，并将已建立的构建块组装成能够执行部分神经元或神经元网络功能的功能亚基。为了调查公众对自下而上的合成生物学和合成神经元的社会影响的看法，该项目将召开审议小组讨论。该研究团队致力于在构建合成细胞、共同培训下一代跨学科科学家以及培养知情和参与的公众方面取得新进展。这项研究结合了实验和建模方法，将解决三个广泛的目标：1)在单个合成神经元中重建动作电位和突触；2)构建具有定义网络组织的合成多神经元系统；3)扩大公共利益，确保对潜在高效益和高风险的合成神经元项目进行负责任的研究和创新。随着合成生物学、微流体、微操作和工程设计的进步，合成神经元将通过将天然离子通道和/或具有特定分子组成的工程蛋白结合在具有特定几何形状的囊泡中来构建。通过这一努力产生的集体知识将通过阐明实现神经元功能的最小组件以及神经元形态如何控制神经元功能来推进神经科学。通过使用工程蛋白和建模辅助开发突触通信的从头机制，将获得对神经元通信设计原则的重要新见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.