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有用生物特性的生物有机体。在任何工程学科中，模块化的概念是成功和具有成本效益的设计的关键。合成生物学在这方面也没有什么不同。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。如果模块的特性很好，就有可能从各个组件预测得到的系统的行为。与电路或机械设备等其他工程系统不同，细胞中发现的生物网络天生就有噪音，因为分子水平上存在随机运动。这个项目的动机来自于先前NSF项目的结果，在该项目中，发现可以利用蜂窝网络中的噪声来获得关于其模块结构的相关信息。这个项目将通过实验来检验这一假设。特别是，将测量模块化程度，并将研究在合成遗传系统中改善模块化的方法，如E.Coli。最后，该项目将描述电路组件本身的特性。这项研究的最终目的是帮助工程师可靠、经济地设计和构建大规模的合成遗传系统。这项研究将为所有级别的学生提供关于网络生物学的新的理论见解和重要的多学科教育和培训机会。广泛的影响：该项目包括为本科生和研究生正在进行的学术课程开发，包括合成生物学课程和关于系统和控制的新课程。此外，由于这项提议，一些本科生、实习生和欧洲交换生将在夏季和冬季得到帮助。作为教育贡献的一部分，一本新的低成本本科教材《生物工程师的系统与控制》将在这项提案的帮助下编写。该项目还将涉及以前的项目之间的密切相互作用，这些项目帮助开发了合成生物学设计软件(TinkerCell)，该软件已经在合成生物学社区和本科教学中广泛使用。拟议的工作将领导合成生物学开放语言(SBOL)社区并向其提供信息。在更广泛的社会背景下，新设计的生物体将能够应对我国面临的一些至关重要的挑战，例如，开发新的高效生物燃料生产方法。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本的科学基础。

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.