Community science designed ribosomes with beneficial phenotypes
Abstract
Functional design of ribosomes with mutant ribosomal RNA (rRNA) can expand opportunities for understanding molecular translation, building cells from the bottom-up, and engineering ribosomes with altered capabilities. However, such efforts are hampered by cell viability constraints, an enormous combinatorial sequence space, and limitations on large-scale, 3D design of RNA structures and functions. To address these challenges, we develop an integrated community science and experimental screening approach for rational design of ribosomes. This approach couples Eterna, an online video game that crowdsources RNA sequence design to community scientists in the form of puzzles, with in vitro ribosome synthesis, assembly, and translation in multiple design-build-test-learn cycles. We apply our framework to discover mutant rRNA sequences that improve protein synthesis in vitro and cell growth in vivo, relative to wild type ribosomes, under diverse environmental conditions. This work provides insights into rRNA sequence-function relationships and has implications for synthetic biology.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 21, 2023
- Source ID
- 10.1038/s41467-023-35827-3
Entities
People
- Alysse Defoe
- Andrew M Watkins
- Anne E. d’Aquino
- Antje Krüger
- Camila Kofman
- Eli Fisker
- Eterna Participants
- Jeff Anderson-Lee
- Jill Townley
- Jonathan Romano
- Michael C Jewett
- Rhiju Das
- Roger Wellington-oguri
- Yejun Kim
Organizations
- Army Research Office
- David and Lucile Packard Foundation
- Foundation for the National Institutes of Health