ERA SynBio: A Unified Nucleic Acid Computation System (UNACS) for Organisms

合成生物学是一门新兴学科，它利用工程原理和计算方法来帮助找到关键生物学问题的答案，并启发可持续的生物制造解决方案，以满足许多社会需求。该项目结合尖端专业知识，创造可编程的、高性能的、基于核酸的调节设备，通过研究细菌的新陈代谢(生命的化学反应)，可以针对特定应用进行优化。这项研究有助于为生命有机体编程的能力奠定基础，并有望在包括纳米技术、绿色技术和生物经济在内的科学和技术领域产生革命性的变化。基于核酸的调控元件通过利用可预测的Watson-Crick碱基配对来控制细胞行为，并利用用于预测分子结构及其相互作用的复杂软件工具，为合成生物学中的关键瓶颈问题提供了解决方案。定向蛋白质进化方面的新进展促使人们研究这些技术在生物体内执行“基于统一核酸的计算”(UNACS)的更广泛的适用性。在这项提案中，该团队建议在活体生物体中确定基于核调节因子的计算的基本原理，并展示复杂的基于核酸的电路在原核生物和高等生物体中用于代谢物控制的应用。这些工具和方法将代表合理设计电路元件的精确配方，这些电路元件在活体生物体中发挥作用，作为生物技术转型的步骤。UNAC有助于标准化、抽象化和可伸缩性。这些都是对生物系统进行真正“工程”和“重新编程”的重要先决条件，这对合成生物学充分发挥其潜力至关重要。该项目通过美国国家科学基金会和欧洲资助机构之间的跨国资助机制提供资金，这些机构是欧洲委员会批准的合成生物学研究区域网络的一部分。该项目的美国部分由系统和合成生物学(生物科学局)和生物技术和生化生物工程(工程局)方案共同资助。

Synthetic Biology is an emerging discipline that distinguishes itself by drawing on engineering principles and computational methods to help find the answers to vital biological questions, and to inspire sustainable biomanufacturing solutions for many societal needs. This project combines cutting-edge expertise to create programmable, high-performance, nucleic acid-based regulatory devices that can be optimized for specific applications through work on a bacterium's metabolism (the chemical reactions of life). This research contributes to the groundwork underlying the ability to program living organisms, and is anticipated to produce transformative changes in science and technology encompassing nanotechnology, green technology, and the bioeconomy. Nucleic-acid-based regulatory elements offer a solution to a critical bottleneck problem in synthetic biology by taking advantage of predictable Watson-Crick base pairing to control cell behavior, and by harnessing sophisticated software tools used to predict molecular structures and their interactions. New developments in directed protein evolution prompted this investigation of the broader applicability of these techniques to perform "Unified Nucleic-Acid based Computation" (UNACS) in living organisms. In this proposal, the team proposes to identify the fundamental principles of riboregulator-based computation in living organisms and to demonstrate the application of complex nucleic-acid based circuits for metabolite control in prokaryotes and higher organisms. These tools and approaches will represent a precise recipe for rational design of circuit elements that function in living organisms as steps towards transformation of biotechnology. UNACS lends itself to standardization, abstraction, and scaling. These are all important pre-requisites for genuine "engineering" and "reprogramming" of biological systems, which are essential for synthetic biology to realize its full potential.This project is funded through a transnational funding mechanism between the United States National Science Foundation and European Funding Agencies that are part of the European Commission endorsed Research Area Network in Synthetic Biology. The United States component of this project was co-funded by programs in Systems and Synthetic Biology (Directorate for Biological Sciences) and Biotechnology and Biochemical Bioengineering (Directorate for Engineering).