How did translation emerge in an RNA world? Ribozymes catalyzing peptide bond formation have been found by directed evolution [1] and very recently using highly conserved small RNA regions at the core of the ribosome [2]. This suggests that an origin of translation is possible from rudimentary RNAs. However, there remains a large gap between catalyzing a single peptide bond and establishing a genetic code.
The project aims to design, screen and evolve ribozymes that catalyze peptide bond formation from a aminoacylated RNAs with substrate specificity. The postdoc will then expand the repertoire of ribozymes and their specific charged RNAs. This should allow reaction networks made of multiple RNA species to catalyze the non-random synthesis of small peptides. In parallel, small peptides that improve ribozyme function will be screened for, with the ultimate goal to establish a positive feedback between peptide products formation and ribozyme catalysis.
The postdoc will benefit from expertise in the lab for directed evolution, microfluidics, sequencing, molecular design using machine learning.
[1] Zhang, B., & Cech, T. R. (1997). Peptide bond formation by in vitro selected ribozymes. Nature, 390(6655), 96-100.
[2] Bose, Tanaya, et al. "Origin of life: Protoribosome forms peptide bonds and links RNA and protein dominated worlds." Nucleic acids research 50.4 (2022): 1815-1828.
Related publications from the lab :
Lu, Heng, et al. "Small-molecule autocatalysis drives compartment growth, competition and reproduction." Nature Chemistry (2023): 1-9.
Reed, Brian D., et al. "Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device." Science 378.6616 (2022): 186-192.
Ameta, Sandeep, et al. "Darwinian properties and their trade-offs in autocatalytic RNA reaction networks." Nature Communications 12.1 (2021): 842.
Arsène, Simon, et al. "Coupled catabolism and anabolism in autocatalytic RNA sets." Nucleic Acids Research 46.18 (2018): 9660-9666.
Matsumura, Shigeyoshi, et al. "Transient compartmentalization of RNA replicators prevents extinction due to parasites." Science 354.6317 (2016): 1293-1296.