Collaborative Research: Life with an RNA Genome

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followed by an RNA/protein world and possibly RNA-based protocells, and leading to present-day cells where RNA has been replaced by DNA as the information source.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