Descrizione del progetto
Approfondimento sulla replicazione dell’acido nucleico indotta chimicamente
La replicazione del DNA rappresenta un importante evento evolutivo in quanto permette agli organismi di passare informazioni genetiche alla loro prole. Tuttavia, la nostra comprensione di come la replicazione dell’acido nucleico sia avvenuta senza enzimi geneticamente codificati è limitata. Il progetto RNA-Rep, finanziato dall’UE, sta testando l’ipotesi che la replicazione non enzimatica dell’RNA possa essere svolta da sostanze chimiche e che la molecola a doppio filamento risultante venga separata tramite riscaldamento. Dato che le alte temperature provocano danni e perdite per le membrane, i ricercatori stanno studiando uno scenario in cui singoli filamenti di RNA vengono inglobati in compartimenti protocellulari. Il progetto fornirà conoscenze senza precedenti sul meccanismo della replicazione nucleica prima dell’inizio dell’evoluzione darwiniana.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesgeneticsnucleotides
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
SN2 1FL Swindon
Regno Unito