Collaborative Research: Life with an RNA Genome

这项研究将通过研究从以RNA为生物信息库的原始世界到以DNA为基础的基因组的第一个细胞的过渡来探索生命的起源。学员将获得染色体规模合成生物学的专业知识，这是一项快速发展的具有变革能力的技术。位于STEM领域、社会科学和修辞学交汇处的教育部分将吸引广泛的学生讨论伦理学和治理方面的紧迫问题，以及塑造科学探究的主题。外展将包括制作非专家可接触的新媒体和深入的书面配套文章。大多数关于生命起源的理论假设RNA世界是自我复制的RNA分子，紧随其后的是RNA/蛋白质世界，可能还有基于RNA的原始细胞，并导致今天的细胞，在那里，RNA已经被DNA作为信息源。从RNA到DNA的转变是至关重要的，但人们对RNA作为细胞基因组的制约因素知之甚少。尽管基于RNA的细胞不再存在于地球上，但RNA病毒可能是前DNA生命的残余物，而RNA生命可能存在于宇宙的其他地方。这项研究将创造新的使能技术，在细菌和真核细胞中启动人工RNA染色体，表征这些宿主内人工RNA染色体的物理稳定性，测量信息传递到子细胞的保真度，最终为基于RNA的基因组的信息能力提供证据。最终目标是在大肠杆菌和酿酒酵母(酵母)宿主体内建立ARCS作为必要的染色体。这些细胞将代表新的人工生命形式，与其他新的和激进的生物(N/RMOS)一起受到公众的极大关注。将对N/RMO的当前治理进行调查，并将建议指导未来研究的伦理和治理原则。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。

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followed by an RNA/protein world and possibly RNA-based protocells, and leading to present-day cells where RNA has been replaced by DNA as the information source.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