Description du projet
Concevoir des interactions biomoléculaires pour les applications acellulaires
Les cellules sont des environnements encombrés, dans lesquels les composants nécessaires sont concentrés dans des compartiments confinés afin d’accroître l’efficacité des processus biologiques. La capacité intrinsèque de nombreuses biomolécules à se regrouper en assemblages denses, connus sous le nom de condensats biomoléculaires, permet de compartimenter davantage les processus biologiques. Ces condensats renforcent les interactions moléculaires, permettant la formation de réactions biochimiques hautement spécifiques et efficaces. Financé par le Conseil européen de la recherche, le projet SYNSEMBL entend créer de nouveaux condensats biomoléculaires en tant que compartiments synthétiques dans des réactions acellulaires. Les chercheurs recourront à la microfluidique et produiront des condensats sur mesure dotés de propriétés et de fonctions spécifiques. En fin de compte, ces condensats biomoléculaires ont des applications potentielles dans les domaines de la science des matériaux et de la biologie synthétique.
Objectif
Compartmentalization is a defining characteristic of life and has the potential to enable and improve engineered manufacturing routes in biotechnology. Many biomolecules like proteins and RNA have the ability to spontaneously cluster in molecularly dense, phase-separated liquid-like assemblies, termed biomolecular condensates. Biomolecular condensates are promising as synthetic compartments in cell-free reactions and living cells because they could provide programmable, self-assembled spatial organization and rapidly appear or dissolve on demand. However, we are still lacking key engineering and characterization tools, a fundamental understanding of how the unique material properties influence internal biochemistry, and strategies to regulate these dynamic molecular assemblies. I have recently discovered that different condensate-forming proteins can be synthesized and assemble into liquid-like droplets in cell-free transcription and translation reactions run in a custom-designed microfluidic device. This project will pioneer cell-free synthesis for the engineering and characterization of biomolecular condensates, and engineer new synthetic compartmentalization strategies for cell-free systems and living cells. First, developing and taking advantage of a highly controlled microfluidic cell-free environment we will generate and characterize new synthetic compartments with tailored properties. Secondly, we will specifically target molecules and reactions into the condensate phase and systematically study how condensate properties influence biological functions. Finally, we will implement dynamic feedback control mechanisms that can autonomously adjust presence and functions of synthetic compartments in cell-free systems and in cells. SYNSEMBL will break new grounds for applications of biomolecular condensates in material science and synthetic biology.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
80333 Muenchen
Allemagne