Community science designed ribosomes with beneficial phenotypes

Area of Science:

• Synthetic Biology
• Molecular Biology
• Biochemistry

Background:

• Designing functional ribosomes with mutant ribosomal RNA (rRNA) is crucial for understanding translation and engineering cellular functions.
• Challenges include cell viability, vast sequence possibilities, and limitations in 3D RNA design.

Purpose of the Study:

• To develop an integrated community science and experimental screening approach for rational ribosome design.
• To discover mutant rRNA sequences that enhance protein synthesis and cell growth.

Main Methods:

• Coupled Eterna, an online RNA design game, with in vitro ribosome synthesis, assembly, and translation.
• Employed multiple design-build-test-learn cycles.

Main Results:

• Identified mutant rRNA sequences that improve in vitro protein synthesis and in vivo cell growth compared to wild-type ribosomes.
• Demonstrated enhanced ribosome function under diverse environmental conditions.

Conclusions:

• The developed framework enables rational design of ribosomes with improved capabilities.
• Provides insights into rRNA sequence-function relationships with implications for synthetic biology and bottom-up cell construction.