Collaborative Research: Toward lifelike synthetic cells via engineered control of DNA replication

细胞可靠地复制和维护基因组信息的能力是生命的一个关键方面。概述这些机制是发展自主合成细胞的关键一步，这些细胞具有自我复制和稳定传播其遗传信息的能力。为此，该项目为合成细胞中的DNA复制控制创造了一种新的合成机制，这将为生物医学和生物技术的新应用打开大门。该项目对当前围绕工程合成细胞技术的监管框架进行了综合社会科学调查。该项目还提供教育和技术培训，旨在增加从事合成细胞研究工作的本科生和毕业生的数量和多样性。与当地合作伙伴一起开展公众宣传，以提高公众对合成电池技术的认识。自然细胞已经进化出复杂的机制来控制DNA复制，以防止关键基因的丢失，同时防止失控的复制。合成细胞需要类似的复制控制机制。虽然天然基因组复制控制系统是复杂的，但质粒提供了一个简单但强大的模块化系统来构建合成复制控制系统和合成细胞的模块化基因组。这个项目解决了为合成细胞系统设计DNA复制控制机制的广泛挑战。RNA工程技术被用来创建模块化和可编程的合成质粒复制控制系统，该系统在细胞和类细胞系统中都能发挥作用。该项目还研究了DNA复制如何被用于新的生物传感应用。生物遏制申请通过综合社会科学调查进行调查。该奖项由分子和细胞生物科学部门的系统和合成生物学集群以及化学、生物工程、环境和运输系统部门的细胞和生化工程计划共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The ability of cells to reliably replicate and maintain genomic information is a key facet of life. Recapitulating these mechanisms is a critical step towards the development of autonomous synthetic cells that exhibit self-replication and stable propagation of their genetic information. To that end, this project creates a new synthetic mechanism for DNA replication control in synthetic cells that will open the door for new applications in biomedicine and biotechnology. This project carries out an integrated social science investigation into the current regulatory framework surrounding engineered synthetic cell technologies. This project also provides educational and technical training aimed at increasing the number and diversity of undergraduates and graduates pursuing careers in synthetic cell research. Public outreach is carried out in conjunction with local partners to increase public awareness of synthetic cell technologies. Natural cells have evolved sophisticated mechanisms to control DNA replication, to prevent the loss of critical genes while simultaneously preventing runaway replication. Analogous replication control mechanisms will be required for synthetic cells. While natural genome replication control systems are complex, plasmids provide a simple yet powerful and modular system for building synthetic replication control systems and modular genomes for synthetic cells. This project addresses the broad challenge of engineering DNA replication control mechanisms for synthetic cell systems. RNA engineering techniques are used to create modular and programmable synthetic plasmid replication control systems that function in both cells and cell-like systems. This project also studies how DNA replication can be utilized for novel biosensing applications. Biocontainment applications are investigated through an integrated social science investigation.This award is co-funded by the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences and the Cellular and Biochemical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.