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: 1935226
• 负责人: Chongli Yuan
• 金额: $ 57万
• 依托单位: Purdue 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 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1935226&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.

构建合成细胞是合成生物学的一个令人兴奋的领域，有机会解开细胞生命的基本设计和组织原则。Liu博士和他的合作团队已经将神经元确定为一种潜在的易处理细胞，可以从头（自下而上）构建。在动物中，神经元将生化信号转换为电动力学，然后再转换回生化信号。该项目旨在构建具有模块化设计的合成神经元和能够重现自然神经元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已知的天然神经元组成中汲取灵感，将它们分成基本的构建块，并通过掺入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合成生物学的看法以及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）设计具有定义网络组织的合成多神经元系统; 3）构建具有定义网络组织的神经元系统。3）扩大公共利益，确保将潜在的高效益和高风险合成神经元项目纳入负责任的研究和创新。通过合成生物学的进步沿着微流体、显微操作和工程设计，将通过在具有限定几何形状的囊泡中掺入具有限定分子组成的天然离子通道和/或工程蛋白质来构建合成神经元。通过这种奋进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支配神经元功能来推进神经科学。通过使用工程蛋白质开发突触通讯的从头机制并辅以建模，将获得对神经元通讯设计原理的重要新见解。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Pre-differentiation exposure to low-dose of atrazine results in persistent phenotypic changes in human neuronal cell lines

分化前暴露于低剂量莠去津会导致人类神经细胞系持续表型变化

• DOI: 10.1016/j.envpol.2020.116379
• 发表时间: 2021
• 期刊: Environmental Pollution
• 影响因子: 8.9
• 作者: Xie, Junkai;Lin, Li;Sánchez, Oscar F.;Bryan, Chris;Freeman, Jennifer L.;Yuan, Chongli
• 通讯作者: Yuan, Chongli

Review: Engineering in situ biosensors for tracking cellular events

• DOI: 10.1016/j.coche.2020.06.006
• 发表时间: 2020-12
• 期刊: Current opinion in chemical engineering
• 影响因子: 6.6
• 作者: Kyle Wettschurack;Junkai Xie;Oscar F. Sánchez;Chongli Yuan

Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons

PFOA 分化前暴露可诱导人类多巴胺能样神经元 DNA 甲基化和线粒体形态的持续变化

• DOI: 10.1016/j.envpol.2022.119684
• 发表时间: 2022
• 期刊: Environmental Pollution
• 影响因子: 8.9
• 作者: Zhao, Han;Xie, Junkai;Wu, Shichen;Sánchez, Oscar F;Zhang, Xinle;Freeman, Jennifer L.;Yuan, Chongli
• 通讯作者: Yuan, Chongli

Identifying distinct heterochromatin regions using combinatorial epigenetic probes in live cells

• DOI: 10.1016/j.bbagrm.2021.194725
• 发表时间: 2021-06-26
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
• 影响因子: 4.7
• 作者: Mendonca，Agnes;Sanchez，Oscar F.;Yuan，Chongli
• 通讯作者: Yuan，Chongli