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

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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).