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

合作研究：合成神经元和可编程神经元网络的自下而上构建

• 批准号: 1934864
• 负责人: Taekjip Ha
• 金额: $ 57万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1934864&HistoricalAwards=false
• 关键词: Collaborative; Research; Bottom; up; Construction

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.

建筑合成细胞是合成生物学的一个令人兴奋的领域，有机会揭示基本设计和细胞生活的组织原理。 Liu博士和他的合作团队已将神经元确定为可以从地面（底部）构建的潜在易于处理的细胞。神经元将生化信号转换为电动动力学，并回到动物中的生化信号。该项目旨在构建具有模块化设计和可编程合成神经元网络的合成神经元，能够概括天然神经元系统的基本功能。该团队的设计方法是从天然神经元的构成中已经知道的东西，将它们分为基本的构件，并通过蛋白质和材料的结合来构建每个构件，并将已建立的构件组装成能够执行一部分神经元或神经元网络功能的功能亚基。为了调查公众对合成神经元的自下而上合成生物学和社会意义的看法，该项目将召集审议小组讨论。研究团队致力于在建立合成细胞，共同培训下一代跨学科科学家，并培养知情和参与的公众方面进行新的基础。这项研究结合了实验性和建模方法，并将解决三个广泛的目标1）将行动潜力和突触重新建立在单个合成神经元中； 2）具有定义网络组织的合成多神经系统； 3）扩大公共利益，并确保将负责任的研究和创新纳入潜在的高效率和高风险合成神经元项目。通过合成生物学的进步以及微流体，微观渗透和工程设计，合成神经元将通过在囊泡中具有定义的分子组成的定义几何形状来构建合成神经元。通过这项努力产生的集体知识将通过阐明最小成分来提高神经科学，以实现神经元功能以及神经形态如何控制神经元功能。通过使用工程蛋白质开发从头开始的突触通信机制并在建模方面，将获得重要的新见解，将获得神经元通信的设计原则。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准来通过评估来获得支持的。

项目成果

Engineering Functional Membrane-Membrane Interfaces by InterSpy.

• DOI: 10.1002/smll.202202104
• 发表时间: 2023-03
• 期刊: SMALL
• 影响因子: 13.3
• 作者: Moghimianavval, Hossein;Patel, Chintan;Mohapatra, Sonisilpa;Hwang, Sung-Won;Kayikcioglu, Tunc;Bashirzadeh, Yashar;Liu, Allen P.;Ha, Taekjip
• 通讯作者: Ha, Taekjip