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

合作研究：通过 DNA 复制的工程控制打造逼真的合成细胞

• 批准号: 2124306
• 负责人: James Chappell
• 金额: $ 37.32万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2124306&HistoricalAwards=false
• 关键词: Collaborative; Research; Toward; lifelike; synthetic

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.

细胞可靠地复制和维持基因组信息的能力是生命的一个关键方面。总结这些机制是迈向自主合成细胞的关键一步，这些细胞表现出自我复制和遗传信息的稳定传播。为此，该项目创造了一种新的合成机制来控制合成细胞中的DNA复制，这将为生物医学和生物技术的新应用打开大门。该项目对目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的本科生和毕业生的数量和多样性。与当地伙伴共同开展公众外展活动，以提高公众对合成细胞技术的认识。自然细胞已经进化出复杂的机制来控制DNA复制，防止关键基因的丢失，同时防止失控的复制。合成细胞也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，但质粒为构建合成复制控制系统和合成细胞的模块化基因组提供了一个简单而强大的模块化系统。该项目解决了合成细胞系统工程DNA复制控制机制的广泛挑战。RNA工程技术用于创建模块化和可编程的合成质粒复制控制系统，该系统在细胞和细胞样系统中都起作用。该项目还研究了DNA复制如何用于新的生物传感应用。通过综合社会科学调查对生物防护应用进行了调查。该奖项由分子和细胞生物科学部的系统和合成生物学集群以及化学、生物工程、环境和运输系统部的细胞和生化工程项目共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

RNA Compensation: A Positive Feedback Insulation Strategy for RNA-Based Transcription Networks

• DOI: 10.1021/acssynbio.1c00540
• 发表时间: 2022-03-18
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Liu, Baiyang;Samaniego, Christian Cuba;Franco, Elisa
• 通讯作者: Franco, Elisa