ERA SynBio: Orthogonal Replication as the Platform for an Episome

该项目涉及美国、法国和英国的6个研究小组。其目标是在活细胞中实现人工、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Episome)。这样的细胞将利用天然遗传物质维持其生长，但当配备适当的合成(外体)系统时，可以制造有用的产品。该项目将对细胞中化学信息的管理产生洞察力(包括自然系统可能进化的方式)，并将立即在代谢工程中应用。从事这个项目的学生和年轻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。将开发一个正交的细菌Episome，基于可以通过工程链接到细胞功能和抗生素耐药性的稳定维持的线性质粒系统。Episome上的遗传信息将由被称为XNAs的合成核酸独家编码。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提供资金，这些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。

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).