Characterizing and Engineering Cellular Networks using Stochastic Measurements

智力优势：合成生物学是一门新的工程学科，旨在设计和构建具有新的和有用的生物学特性的生物有机体。在任何工程学科中，模块化的概念是成功和经济有效的设计的关键。合成生物学在这方面也不例外。模块化使工程师能够以可预测的方式从较小的组件构建更大的系统。如果模块被很好地表征，就有可能从单个组件预测最终系统的行为。与电路或机械装置等其他工程系统不同，细胞中的生物网络本身就存在噪声，因为在分子水平上存在随机运动。这个项目的动机来自于以前的NSF项目的结果，该项目发现蜂窝网络中的噪声可以被利用来获得有关其模块化结构的相关信息。这个项目将通过实验来验证这个假设。特别是模块化的程度将被测量，并提高模块化的方法将研究在合成遗传系统，如大肠杆菌。最后，该项目将描述电路元件本身。这项研究的最终目的是帮助工程师可靠和经济有效地设计和构建大规模的合成遗传系统。本研究将为网络生物学提供新的理论见解，并为各层次学生提供重要的多学科教育和培训机会。更广泛的影响：该项目包括正在进行的本科生和研究生的学术课程开发，包括合成生物学课程和系统与控制的新课程。此外，由于这项建议，一些本科生、实习生和欧洲交换学生将在夏季和冬季得到帮助。作为教育贡献的一部分，将在此提案的帮助下编写一本新的低成本本科教科书“生物工程师系统与控制”。该项目还将涉及与先前帮助开发合成生物学设计软件（TinkerCell）的项目之间的密切互动，该软件已广泛应用于合成生物学社区和本科教学。拟议的工作将引导和通知合成生物学开放语言（SBOL）社区。在更广泛的社会背景下，新设计的生物将能够解决我们国家面临的一些至关重要的挑战，例如，开发新的有效的生物燃料生产方法。此外，合成生物学将有助于为未来一系列全新的生物技术产业奠定基础。

Intellectual Merit: Synthetic biology is a new engineering discipline that aims to design and construct biological organisms that exhibit new and useful biological properties. In any engineering discipline, the concept of modularity is the key to successful and cost-effective design. Synthetic biology is no different in this regard. Modularity enables engineers to construct, in a predicable fashion, larger systems from smaller components. If the modules are well characterized, it is possible to predict the behavior of the resultant system from the individual components. Unlike other engineered systems such as electrical circuits or mechanical devices, biological networks found in cells are inherently noisy because there is random motion at the molecular level. This project is motivated by results from a previous NSF project where it was found that noise in cellular networks can be exploited to obtain relevant information about their modular structure. This project will test this hypothesis experimentally. In particular the degree of modularity will be measured, and methods for improving modularity will be investigated in synthetic genetic systems such as E.coli. Finally, the project will characterize the circuit components themselves. The ultimate aim of this research is to help engineers reliably and cost-effectively design and construct large-scale synthetic genetic systems. This study will provide new theoretical insights into network biology and important multi-disciplinary educational and training opportunities for students at all levels.Broader Impacts: This project includes ongoing academic curricula development for undergraduate and graduate students, including courses on synthetic biology and new courses on systems and control. Furthermore, a number of undergraduates, interns, and European exchange students will be assisted as a result of this proposal during the summer and winter months. As part of the educational contribution, a new low cost undergraduate text book "Systems and Control for Bioengineers" will be written with the aid of this proposal. The project will also involve a close interplay between previous projects which helped develop design software for synthetic biology (TinkerCell) already widely used in the synthetic biology community and undergraduate teaching. The proposed work will lead and inform the Synthetic Biology Open Language (SBOL) community. In the broader societal context, newly designed organisms will be able to address a number of critically important challenges to our nation, for example, the development of novel and efficient ways for biofuel production. Furthermore, synthetic biology will help lay the basic scientific foundation for an entirely new range of future biotechnology industries.