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.
