Engineering Synthetic Multicellular Systems

合成生物学将从根本上改变分子医学的性质，正如人类工程师所了解的那样。 如何构建和编程细胞。这些先进的工程技术将帮助我们了解发展 处理并将这种理解用于组织工程、生物制造、生物传感等。的 然而，现实目前并没有梦想那么令人兴奋：编程细胞行为构成了巨大的技术挑战。 概念上的挑战。拟议中的研究旨在迈出重要的第一步， 设计细胞间通讯途径并协调基因表达和行为 细胞群这些合成通信系统利用来自细菌的天然成分， “群体感应”系统，但以新的方式组装它们，使人类能够控制人口如何 它的发展以及最终的作用 许多细胞的协调活动通常是复杂的生物行为所必需的，包括 发育、生物膜形成或群体行为。每个细胞与其邻居的相互作用， 简单的局部规则，这些相互作用共同产生所需的全球时空行动。的 所提出的工作的最终目的是构建表现出这种能力的合成细菌系统， 完全由合成电路编程为了实现这一目标，研究还将建立框架， 工程蜂窝间通信网络，包括适当的数学描述， 信号扩散和细胞反应，以及新的组件，将允许细胞的感觉， 对多种化学信号作出反应。开发的特定通信组件和子电路 这项研究预计可转移到其他生物体，包括哺乳动物细胞。这 协作项目是独一无二的，它结合了几十年来从计算机中收集到的“理性”设计原则 工程和生物研究与实验室进化，可以微调粗糙的人类设计 并制造出运行顺畅的合成通信网络。

Synthetic biology will fundamentally change the nature of molecular medicine, as human engineers learn how to build and program cells. These forward engineering efforts will help us understand developmental processes and use that understanding for tissue engineering, biofabrication, biosensing, and more. The reality, however, is currently less exciting than the dream: programming cell behavior poses huge technical and conceptual challenges. The proposed research is designed to take important first steps towards engineering intercellular communications pathways and coordinating gene expression and behavior across cell populations. These synthetic communications systems utilize natural components from bacterial 'quorum-sensing' systems, but assemble them in new ways to allow human control over how a population develops and eventually what it does. The coordinated activity of many cells is often required for complex biological behaviors, including development, biofilm formation, or swarm behaviors. Each cell interacts with its neighbors according to simple local rules, and collectively these interactions yield the desired global spatiotemporal actions. The ultimate aim of the proposed work is to build a synthetic bacterial system that exhibits such a capability, entirely programmed in a synthetic circuit. Towards this goal, the research will also build the framework for engineering intercellular communications networks, including appropriate mathematical descriptions of signal diffusion and cellular responses, as well as novel components that will allow cells to sense and respond to multiple chemical signals. Specific communications components and sub-circuits developed in this research are anticipated to be transferable to other organisms, including mammalian cells. This collaborative project is unique in combining 'rational' design principles gleaned from decades of computer engineering and biological research with laboratory evolution, which can fine-tune rough human designs and make smoothly-functioning synthetic communications networks.