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，有机会揭开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易于处理的细胞，可以从头开始构建。在动物体内，神经元将生化信号转换成电动力学，然后再转换回生化信号。该项目旨在构建一个模块化设计的合成神经元和一个能够概括自然神经系统基本功能的可编程合成神经元网络。该团队的设计方法是从天然神经元的组成中获得已知的灵感，将它们划分为基本的构建块，并通过结合蛋白质和材料来构建每个构建块，并将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的看法和合成神经元的社会影响，该项目将召集审议小组讨论。该研究团队致力于在构建合成细胞方面开辟新的天地，共同培养下一代跨学科科学家，并培养知情和参与的公众。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)设计具有明确网络组织的合成多神经元系统；以及3)扩大公共利益，并确保将其纳入潜在高收益和高风险合成神经元项目的负责任的研究和创新中。在合成生物学的进步以及微流体、微操作和工程设计的推动下，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整合到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成部分以及神经元形态如何管理神经元功能来促进神经科学。通过使用工程蛋白开发突触通信的从头机制并辅助建模，将对神经元通信的设计原则获得重要的新见解。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.