Description du projet
Aperçu de la réplication des acides nucléiques induite par la chimie
La réplication de l’ADN représente un événement évolutif majeur, car elle permet aux organismes de transmettre des informations génétiques à leur progéniture. Cependant, nous comprenons encore mal comment la réplication de l’acide nucléique s’est produite sans enzymes génétiquement codées. Le projet RNA-Rep, financé par l’UE, teste l’hypothèse selon laquelle la réplication non enzymatique de l’ARN peut être prise en charge par des produits chimiques et qu’un réchauffement permet de séparer la molécule double brin résultante. Puisque les températures élevées endommagent la membrane et provoquent des fuites, les chercheurs étudient le scénario selon lequel des brins simples d’ARN sont englobés dans des compartiments protocellulaires. Le projet fournira des connaissances sans précédent sur le mécanisme de réplication nucléique avant le début de l’évolution darwinienne.
Objectif
Deciphering how nucleic acids replicated in the absence of genetically encoded enzymes is of critical importance to understanding the onset of Darwinian evolution. While much effort has been put into developing chemically-driven copying of RNA exploiting activated monomers, many unsolved issues stand in the way of achieving repeated cycles of non-enzymatic RNA replication. Non-enzymatic copying of a template strand results in the formation of an RNA duplex, which must then be denatured in order for subsequent rounds of replication to take place. Although RNA strands can be separated by heating, re-annealing kinetically outcompetes slow non-enzymatic copying, thus inhibiting RNA amplification. One unexplored solution to this problem is to physically separate melted strands of RNA so that re-annealing is not possible. Since all known living systems exploit lipid membranes, we propose to investigate whether protocellular compartments can facilitate the emergence of simplistic chemical systems that amplify RNA. Specifically, high temperatures are known to induce both RNA strand separation and bilayer defects, ultimately allowing for the partial leakage of RNA. If the transition temperature of the lipid membrane is higher than the melting temperature of the RNA, then subsequent slow cooling would recover the original impermeability of the membrane and give rise to a fraction of protocellular structures containing stochastic numbers of single RNA strands. At this stage, feeding with permeable activated short (oligo)nucleotides would lead to renewed copying of RNA. This highly original and multidisciplinary project combines the strength of organic and supramolecular chemistry to optimise prebiotic compartments with the power of in situ non-enzymatic RNA biochemistry to yield a project of excellent, innovative science that will exploit my expertise in protocellular systems while providing me extensive training in organic synthesis, chemical biology and biophysics.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesgeneticsnucleotides
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
SN2 1FL Swindon
Royaume-Uni