Collaborative Research: Life with an RNA Genome

合作研究：RNA 基因组的生命

• 批准号: 1935366
• 负责人: Jef Boeke
• 金额: $ 129.3万
• 依托单位: New York University Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1935366&HistoricalAwards=false
• 关键词: Collaborative; Research; Life; RNA; Genome

This research will explore origins-of-life by studying the transition from a primordial world in which RNA served as the repository of biological information to the first cells with DNA-based genomes. Trainees will gain expertise with chromosome-scale synthetic biology, a rapidly developing technology with transformative capabilities. Educational components situated at the intersection of STEM fields, social sciences, and rhetoric will engage a broad cohort of students discussing pressing issues in ethics and governance and the themes that shape scientific inquiry. Outreach will involve production of new media accessible to non-experts paired with in-depth written companion articles.Most theories of the origins-of-life posit an RNA world of self-replicating RNA molecules, followed by an RNA/protein world and possibly RNA-based protocells, and leading to present-day cells where RNA has been replaced by DNA as the information source. The transition from RNA to DNA is crucial, yet little is known about the constraints of RNA as a cellular genome. Although RNA-based cells no longer exist on Earth, RNA viruses may be remnants of pre-DNA life, and RNA life may exist elsewhere in the universe. This research will create new enabling technologies to launch artificial RNA chromosomes (ARCs) in bacterial and eukaryotic cells, characterize the physical stability of ARCs inside these hosts, measure the fidelity of information transmission to daughter cells, and finally provide evidence for the information capacity of RNA-based genomes. The ultimate goals are to establish ARCs as essential chromosomes within E. coli and S. cerevisiae (yeast) hosts. These cells would represent new forms of artificial life, which along with other novel and radically modified organisms (N/RMOs) are of great public interest. The current governance of N/RMOs will be surveyed, and ethics and governance principles that should guide future research will be recommended.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.

这项研究将通过研究从原始世界的过渡来探索生命的起源，在该世界中，RNA充当了生物学信息的存储库，向具有基于DNA的基因组的第一个细胞。学员将获得染色体规模合成生物学的专业知识，这是一种具有变革能力的快速发展的技术。位于STEM领域，社会科学和言论的交集的教育组成部分将吸引大量的学生讨论道德和治理中的紧迫问题以及塑造科学探究的主题。外展活动将涉及可与非专家访问的新媒体以及深入的书面同伴文章配对。生命原产的大多数理论构成了一个自我复制的RNA分子的RNA世界，随后是RNA/蛋白质世界以及可能的基于RNA的Proteocells，并导致RNA由RNA替换为RNA的替换为DNA的替代。从RNA到DNA的过渡至关重要，但对RNA作为细胞基因组的约束知之甚少。尽管基于RNA的细胞不再存在于地球上，但RNA病毒可能是DNA前寿命的残留物，RNA寿命可能存在于宇宙其他地方。这项研究将创造新的促成技术，以在细菌和真核细胞中发射人造RNA染色体（ARC），表征这些宿主内部电弧的物理稳定性，测量信息传播到子细胞的忠诚度，并最终提供基于RNA基因组信息能力的证据。最终的目标是将弧建立为大肠杆菌和酿酒酵母（酵母）宿主内的基本染色体。这些细胞将代表新形式的人造生命，这些生命与其他新颖和根本修改的生物（N/RMO）具有极大的公共利益。 N/RMO的当前治理将进行调查，应推荐应指导未来研究的道德和治理原则。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估审查标准来通过评估来支持的。