Collaborative Research: Life with an RNA Genome

这项研究将通过研究从RNA作为生物信息储存库的原始世界到具有dna基因组的第一个细胞的转变来探索生命的起源。学员将获得染色体规模合成生物学的专业知识，这是一项具有变革能力的快速发展技术。位于STEM领域，社会科学和修辞学交叉点的教育部分将吸引广泛的学生群体讨论道德和治理方面的紧迫问题以及塑造科学探究的主题。外展将包括制作新媒体，非专家可以访问，并搭配深入的书面配套文章。大多数关于生命起源的理论都假设一个RNA世界是由自我复制的RNA分子组成的，然后是RNA/蛋白质世界，可能还有基于RNA的原始细胞，最后导致了现在的细胞，RNA已经被DNA取代，成为信息来源。从RNA到DNA的转变是至关重要的，但很少有人知道RNA作为细胞基因组的限制。虽然地球上不再存在基于RNA的细胞，但RNA病毒可能是前dna生命的残余，而RNA生命可能存在于宇宙的其他地方。本研究将创造新的使能技术，在细菌和真核细胞中发射人工RNA染色体（arc），表征这些宿主体内arc的物理稳定性，测量信息传递给子细胞的保真度，并最终为RNA基因组的信息容量提供证据。最终目标是在大肠杆菌和酿酒酵母宿主中建立arc作为必需染色体。这些细胞将代表人工生命的新形式，它们与其他新颖的和彻底改造的生物（N/RMOs）一起引起了公众的极大兴趣。将调查N/ rmo的当前治理，并建议指导未来研究的伦理和治理原则。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。

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followed by an RNA/protein world and possibly RNA-based protocells, and leading to present-day cells where RNA has been replaced by DNA as the information source.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.