Descripción del proyecto
Ingeniería de interacciones biomoleculares para aplicaciones sin células
Las células son entornos rebosantes y, para aumentar la eficacia de los procesos biológicos, los componentes necesarios se concentran en compartimentos cerrados. La capacidad intrínseca de muchas biomoléculas de agruparse en densos conjuntos, denominados «condensados biomoleculares», permite una mayor compartimentación de los procesos biológicos. Estos condensados potencian las interacciones moleculares y permiten la formación de reacciones bioquímicas altamente específicas y eficaces. El objetivo del proyecto SYNSEMBL, financiado por el Consejo Europeo de Investigación, es diseñar nuevos condensados biomoleculares como compartimentos artificiales en reacciones sin células. Los investigadores emplearán la microfluídica y producirán condensados a medida con propiedades y funciones específicas. En última instancia, estos condensados biomoleculares podrían tener aplicaciones en la ciencia de materiales y la biología sintética.
Objetivo
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.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
80333 Muenchen
Alemania