Projektbeschreibung
Erkenntnisse zur chemisch gesteuerten Nukleinsäure-Replikation
Die DNA-Replikation ist ein wichtiges evolutionäres Ereignis, da sie es Organismen ermöglicht, genetische Informationen an ihre Nachkommen weiterzugeben. Unser Verständnis vom Ablauf der Nukleinsäure-Replikation ohne genetisch kodierte Enzyme ist jedoch gering. Das EU-finanzierte Projekt RNA-Rep testet die Hypothese, dass die nicht-enzymatische RNA-Replikation mittels Chemikalien erfolgen kann und dass das resultierende doppelsträngige Molekül durch Erhitzen getrennt wird. Da hohe Temperaturen Membranschäden und Durchsickerungen induzieren, untersuchen die Forschenden das Szenario, dass einzelne RNA-Stränge in protozellulären Kompartimenten eingeschlossen sind. Das Projekt wird beispiellose Erkenntnisse über den Mechanismus der Nuklein-Replikation vor dem Beginn der darwinistischen Evolution liefern.
Ziel
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.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesgeneticsnucleotides
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
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Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF-EF-ST - Standard EFKoordinator
SN2 1FL Swindon
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