ERA SynBio: Orthogonal Replication as the Platform for an Episome

该项目由美国、法国和英国的6个研究小组参与。目标是在活细胞中实现合成的非天然遗传物质（核酸）的稳定维持和繁殖，而不整合到宿主细胞的遗传物质中。合成的遗传物质将具有与天然遗传物质不同的化学特征，并将在细胞中构成一个单独的、独立的元素（称为片段）。这样的细胞将使用天然遗传物质维持其生长，但如果同时配备适当的合成（episomal）系统，则可以制造有用的产品。这个项目将产生对细胞中化学信息管理的见解（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。基于线性质粒系统的正交细菌集体将被开发出来，该系统可以通过与细胞功能和抗生素耐药性的工程链接来稳定地维持。片段体上的遗传信息将完全由合成核酸编码，称为XNAs。这些XNAs已被证明是无毒的，不能与细胞遗传物质相互作用。国际合作伙伴带来了互补的专业知识，为构建正交系统提供必要的元素和功能。该项目是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的，欧洲资助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与合成生物学（生物科学理事会）和生物技术与生化生物工程（工程理事会）的项目共同资助。

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).