ERA SynBio: Orthogonal Replication as the Platform for an Episome

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This project engages 6 research groups in the United States, France and the United Kingdom. The goal is to achieve the stable maintenance and propagation of synthetic, non-natural genetic material (nucleic acids) in living cells, without integration into the genetic material of the host cell. The synthetic genetic material will have chemical features distinct from natural genetic material and will constitute a separate, independent element (called an episome) in the cell. Such a cell will sustain its growth using the natural genetic material but can make useful products when equipped with the appropriate synthetic (episomal) system in parallel. This project will generate insights into the management of chemical information in cells (including the manner in which natural systems may have evolved) and will have immediate applications in metabolic engineering. The students and young scientists working on this project will have broad and diverse international and transdisciplinary training in molecular genetics, biochemistry and bioengineering. An orthogonal bacterial episome will be developed, based on the linear plasmid system that can be stably maintained through engineered links to cellular functions and antibiotic resistance. The genetic information on the episome will be exclusively encoded by synthetic nucleic acids, termed XNAs. These XNAs have been shown to be non-toxic and unable to interact with the cellular genetic material. The international collaborators bring the complementary expertise to furnish the elements and functionalities that are necessary to build the orthogonal system. 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).