ERA SynBio: Orthogonal Replication as the Platform for an Episome

该项目涉及美国、法国和联合王国的6个研究小组。目标是实现合成的非天然遗传物质（核酸）在活细胞中的稳定维持和繁殖，而不整合到宿主细胞的遗传物质中。合成遗传物质将具有不同于天然遗传物质的化学特征，并将在细胞中构成单独的独立元件（称为附加体）。 这样的细胞将使用天然遗传物质维持其生长，但当与适当的合成（附加型）系统平行配备时，可以产生有用的产物。该项目将深入了解细胞中化学信息的管理（包括自然系统可能进化的方式），并将立即应用于代谢工程。参与该项目的学生和青年科学家将在分子遗传学、生物化学和生物工程方面接受广泛和多样化的国际和跨学科培训。将基于线性质粒系统开发正交细菌附加体，该系统可以通过与细胞功能和抗生素耐药性的工程连接稳定维持。附加体上的遗传信息将仅由称为XNA的合成核酸编码。这些XNA已被证明是无毒的，不能与细胞遗传物质相互作用。 国际合作者带来了互补的专业知识，以提供建立正交系统所必需的元素和功能。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资助，这些机构是欧洲委员会认可的合成生物学研究领域网络的一部分。该项目的美国部分由系统和合成生物学（生物科学理事会）以及生物技术和生物化学工程（工程理事会）方案共同资助。

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).