Descripción del proyecto
Información sobre la replicación de ácidos nucleicos por medios químicos
La replicación del ADN representa un evento evolutivo importante, ya que permite transmitir información genética a la descendencia. Sin embargo, no se sabe a ciencia cierta cómo se produjo la replicación del ácido nucleico sin enzimas codificadas genéticamente. El proyecto RNA-Rep, financiado con fondos europeos, prueba la hipótesis de que la replicación del ARN no enzimático puede adaptarse mediante productos químicos y que la molécula bicatenaria resultante se separa mediante calentamiento. Dado que las altas temperaturas inducen daños en la membrana y fugas, los investigadores están investigando el escenario en que las hebras individuales de ARN están englobadas en compartimentos protocelulares. El proyecto proporcionará un conocimiento sin precedentes sobre el mecanismo de replicación nucleica previo a la evolución darwiniana.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesgeneticsnucleotides
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
SN2 1FL Swindon
Reino Unido