Community science designed ribosomes with beneficial phenotypes

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. While the ribosome has been harnessed for synthetic biology, designing ribosomes has remained challenging. Here, the authors demonstrate a community science approach for rational design of ribosomes with beneficial properties.

Automated summary

By integrating community science and experimental screening, the authors have developed a method for rational design of ribosomes with beneficial properties. They use an online video game, Eterna, to crowdsource RNA sequence design and apply their framework to discover mutant rRNA sequences that improve protein synthesis and cell growth. This work provides insights into rRNA sequence-function relationships and has implications for synthetic biology.