Description du projet
Des cellules synthétiques basés sur des origami d’ARN
Les cellules synthétiques, ou cellules artificielles ou encore protocellules, sont des structures créées en laboratoire qui imitent certaines des propriétés et des fonctions des cellules naturelles. Elles ont suscité un vif intérêt dans le cadre de l’administration de médicaments, de la biotechnologie et de la détection environnementale, ainsi que pour leur implication dans les progrès de la recherche biomédicale. Financé par le Conseil européen de la recherche, le projet ENSYNC ambitionne de construire une cellule synthétique en encapsulant des biomolécules fonctionnelles dans des vésicules lipidiques. L’objectif est concevoir une cellule synthétique autoreproductible et évolutive grâce à des structures d’origami d’ARN programmables, qui dirigent l’évolution et sont fonctionnalisées pour effectuer diverses tâches. Le projet permettra non seulement de mieux comprendre les processus évolutifs, mais également de créer des outils basés sur des origami d’ARN pour diverses applications.
Objectif
Can we construct a cell from non-living matter? In search for answers, bottom-up synthetic biology has successfully encapsulated functional sets of biomolecules inside lipid vesicles, yet a “living” synthetic cell remains unattained. ENSYNC aims for a prototype of a synthetic cell that encompasses a fundamental characteristic of life, namely evolution. My past work shows that DNA origami can achieve custom-engineered synthetic cellular parts, but the mere encapsulation of preformed parts conflicts with the vision of a self-replicating and evolving synthetic cell. I here propose to produce and to replicate functional RNA origami structures inside of lipid vesicles (GUVs) by co-transcriptional folding from a DNA template. First, I will genetically encode an RNA nanopore and RNA origami structure which induces GUV division. The DNA template (“genotype”) will determine the GUVs’ permeability and their division rate (“phenotype”). This genotype-phenotype mapping is the basis for directed evolution of the rationally engineered RNA origami structures in the second step. In particular, I will aim for efficient GUV division in repeated cycles of genetic diversification and selection. In the third step, I will implement multiple growth and division cycles to enable continuous directed evolution. This will be achieved by system-level integration and laboratory automation of the directed evolution pipeline to iteratively reduce researcher intervention. Depending on externally applied selection pressures, continuous evolution will inevitably lead to the dominance of highly proliferating synthetic cells in mixed populations. ENSYNC provides fundamental insights into evolutionary processes as well as applicable RNA origami-based tools for nanopore sensing and as genetically encoded biophysical probes in cell biology. Overall, ENSYNC pushes the boundaries of bottom-up synthetic biology to the point where synthetic cells can be evolved towards a distinct goal in biotechnology.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
69117 Heidelberg
Allemagne