Descripción del proyecto
Células sintéticas con origami de ARN
Las células sintéticas, también conocidas como células artificiales o protocélulas, son estructuras creadas en laboratorio que imitan algunas de las propiedades y funciones de las células naturales. Han despertado un gran interés por su aplicación en la administración de fármacos, la biotecnología y la detección medioambiental, así como para avanzar en la investigación biomédica. Financiado por el Consejo Europeo de Investigación, el equipo del proyecto ENSYNC pretende desarrollar una célula sintética encapsulando biomoléculas funcionales en el interior de vesículas lipídicas. El objetivo es conseguir una célula sintética autorreplicante y evolutiva mediante estructuras de origami de ARN programables, que dirijan la evolución y estén funcionalizadas para realizar distintas tareas. Además de conocimientos sobre los procesos evolutivos, en el proyecto se generarán herramientas basadas en el origami de ARN para diversas aplicaciones.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
69117 Heidelberg
Alemania