CORE+: Chemical and biophysical investigation Of Ribosome Emergence

Project type: Charles University Mini-grant 2023

Flagship: Flagship 4

Project leader at CU: Mgr. Klára Hlouchová, Ph.D. (Faculty of Science)

Participating universities: Sorbonne University, University of Milan

Ribosome, the protein synthesis macromolecular machine, undisputedly lies at the very origin of today’s variety of life. Its complex of RNA strands and proteins, and in particular its catalytic core Peptidyl Transferase Center (PTC), has been proposed a molecular fossil of early life. CORE+ builds on the previous 4EU+ CORE project to investigate the key chemical and biophysical phenomena at the basis of the emergence of nucleotide and peptide sequences, and the processes that may have led to their functional co-assembly in PTC, like spontaneous liquid-liquid phase separation, conformational transitions and ligation reactions. Three complementary teams provide their expertise and tools: biochemistry and synthetic biology in Prague, biophysical characterization in Milano and computer simulations at Sorbonne.

Starting from current PTC, the team will experimentally investigate how patterns of nucleotide and peptide sequences and their folding affect – and are affected by – formation of complexes and demixing, leading to high local concentration and to the emergence of catalytic capability and polymerization. Novel simulation approaches, including AI tools, will allow to model such phenomena from the atomic to the macromolecular up to the polymeric scale.