EAGER: TelePathy: Telecommunication Systems Modeling and Engineering of Cell Communication Pathways

这个EAGER项目由系统和合成生物学项目资助，将导致工具的开发，使研究人员能够操纵细胞（主要是微生物）的行为或状态，用于特定目的或应用。研究人员将利用电信和计算机网络理论以及工程原理来描述和模拟细胞通信网络的功能和动态。这项基础性的重要研究，如果成功，将为细胞如何沟通提供一个新的视角，并将使模拟和设计网络通过细胞行为修改来执行有用的功能，如制造化学品，分布式环境生物传感，以及控制细胞增殖和有害状态。这种跨学科的努力将为各级学生和博士后提供有价值的培训。首席研究员将与社会科学家和伦理学家一起开发一门课程，以解决这项工作，以及一般的合成生物学，将如何影响整个社会。研究人员还将指导一组大学生参加国际基因工程机器竞赛。对于合成生物学和计算机网络工程来说，分析、建模和利用细胞通信系统的工具的开发仍然是一个未开发的途径。该项目的目标是开发基于电信工程原理的定量模型，并通过应用电信度量来定义和操纵单元之间的信息交换。这将通过追求四个目标来实现：(1)开发一个建模框架，该框架将允许从公共数据库识别细胞通信途径及其化学和物理参数；(2)这些细胞通信途径的电信指标表征，特别是关注目前表征不佳的共生微生物系统；(3)基于COMSOL Multiphysics软件平台的计算机仿真框架的开发，以验证所开发的模型，并允许在受控的硅环境中进一步表征它们；(4)设计和优化基于两种人类肠道微生物（即史密斯甲烷预防杆菌和拟杆菌）共生的人工细胞通信系统，这将是使用所开发模型开发能够可靠交换人工信息的生物细胞通信系统的概念证明。

This EAGER project, funded by the Systems and Synthetic Biology program, will lead to the development of tools that will allow researchers to manipulate the behavior or state of cells, mostly microbes,for specific purposes or applications. The investigators will characterize and simulate the functions and dynamics of cell-communication networks using telecommunications and computer networks theory, and engineering principles. This fundamentally important research, if successful, will provide a novel perspective of how cells communicate, and will enable the simulation and the design of networks through cell behavior modification to perform useful functions such as the manufacture of chemicals, distributed environmental bio-sensing, and the control of cell proliferation and harmful states. This strongly interdisciplinary effort will offer valuable training for students and postdoctoral associates at all levels. The principle investigator will develop a course together with social scientists and ethicist to address how this work, and synthetic biology in general, will affect society as whole. The investigators will also mentor a team of undergraduates to participate in the International Genetically Engineered Machine competition. The development of tools to analyze, model, and exploit cell-communication systems remains an unexplored avenue for both synthetic biology and computer network engineering. The goal of this project is to develop quantitative models based on telecommunications engineering principles, and by applying telecommunications metrics, to define and manipulate the exchange of information among cells. This will be achieved by pursuing four objectives: (1) the development of a modeling framework that will allow the identification of cell-communication pathways, and their chemical and physical parameters, from public databases; (2) the telecommunications metrics characterization of these cell-communication pathways, in particular focusing on currently poorly characterized syntrophic microbial systems; (3) the development of a computer simulation framework based on the COMSOL Multiphysics software platform to enable the validation of the developed models, and allow their further characterizations in a controlled in-silico environment; (4) the design and optimization of an artificial cell-communication system based on the syntrophy between two human gut microbes, i.e., Methanobrevibacter smithii and Bacteroides thetaiotaomicron, which will be a proof-of-concept of using the developed models to develop biological cell-communication systems able to reliably exchange artificial messages.