Community science designed ribosomes with beneficial phenotypes

Antje Krüger, Andrew M. Watkins, Roger Wellington-Oguri, Jonathan Romano, Camila Kofman, Alysse DeFoe, Yejun Kim, Jeff Anderson-Lee, Eli Fisker, Jill Townley, Anne E. d’Aquino, Rhiju Das () and Michael C. Jewett ()
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Antje Krüger: Northwestern University
Andrew M. Watkins: Stanford University
Roger Wellington-Oguri: Eterna Massive Open Laboratory
Jonathan Romano: Stanford University
Camila Kofman: Northwestern University
Alysse DeFoe: Northwestern University
Yejun Kim: Northwestern University
Jeff Anderson-Lee: Eterna Massive Open Laboratory
Eli Fisker: Eterna Massive Open Laboratory
Jill Townley: Eterna Massive Open Laboratory
Anne E. d’Aquino: Northwestern University
Rhiju Das: Stanford University
Michael C. Jewett: Northwestern University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-35827-3

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