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RNA-protein Nanostructures for Synthetic Biology

Description du projet

Architectures ARN-protéines au repliement programmable dans les cellules

La nanotechnologie de l’ADN utilise des acides nucléiques artificiels pour créer des nanostructures d’ADN destinées à des applications telles que l’administration de médicaments et le diagnostic. La biologie synthétique est axée sur la réingénierie des organismes et de leurs processus. Cependant, elle ne peut pas tirer parti des méthodes d’assemblage de l’ADN mises au point pour les nanotechnologies de l’ADN, car celles-ci ne sont pas compatibles avec une utilisation dans les cellules. Le projet RNA ORIGAMI, financé par le Conseil européen de la recherche, s’appuiera sur sa méthode révolutionnaire de l’«origami d’ARN» pour concevoir une architecture générale ARN-protéines compatible avec le repliement pendant la synthèse. L’équipe utilisera une approche de conception rationnelle pour programmer le processus de repliement, exprimer les nanostructures ARN-protéines dans les cellules et démontrer leur application en biologie synthétique.

Objectif

Synthetic biology aims at re-engineering organisms for practical applications by designing novel biomolecular components, networks, and pathways. The field is expected to lead to cheaper drugs, sustainable fuel production, efficient diagnosis and targeted therapies for diseases. However, a major obstacle to achieve these goals is our limited ability to rationally design biomolecular structure and function. By contrast, the field of DNA nanotechnology has so far demonstrated an unprecedented ability to design and self-assemble well-defined molecular shapes, although the production method of thermal annealing is not compatible with cells. We have recently demonstrated a breakthrough method, called RNA origami, which allows the design of RNA molecules that fold into well-defined nanoscale shapes during their synthesis by an RNA polymerase. In this proposal I aim at extending this technology to produce RNA-protein nanostructures and at demonstrating their application in synthetic biology. My primary scientific hypothesis is that understanding the folding process during synthesis will help us to design nanostructures that can be produced in cells. I will design a general RNA-protein architecture that is compatible with folding during synthesis. I will investigate folding kinetics to be able to design and program the dynamical folding process. Based on this, RNA-protein nanostructures will be designed, expressed in cells, and verified, for the formation of the desired shapes. We will develop new functionalities by both rational design and selection approaches with the aim of obtaining multivalent-binding and switching properties. Finally, the functional RNA-protein nanostructures will be applied in proof-of-concept experiments to demonstrate efficient, multivalent targeting of subcellular structures, biosensing of a variety of intracellular analytes, metabolic channeling of biosynthesis pathways, and complex control of transcriptional networks.

Régime de financement

ERC-COG - Consolidator Grant

Institution d’accueil

AARHUS UNIVERSITET
Contribution nette de l'UE
€ 1 999 935,00
Adresse
NORDRE RINGGADE 1
8000 Aarhus C
Danemark

Voir sur la carte

Région
Danmark Midtjylland Østjylland
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 999 935,00

Bénéficiaires (1)