Phase separation in multicomponent systems of co-transcriptionally-folded RNA nanostructures: towards autonomous synthetic cell cycles

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Autonomous replication is the hallmark of biological cellular life and recapitulating it in systems constructed from the bottom-up represents the core objective of synthetic cell science. Past attemptsto construct self-replicating synthetic systems from the bottom-up either demonstrated duplication of genetic information or growth and division of cell-like compartments, but the ability to integrate these key processes as seen in extant life-forms is still lacking. With this project, we address this bottleneck with a solution that dovetails the toolkit of nucleic-acid nanotechnology with principles of molecular biology and biophysics. The synthetic cells will form and grow from RNA building blocks transcribed from DNA templates ("genome"). Division and genome segregation will result from phase separation, while genome replication (amplification) will be underpinned by reverse transcription. Because the nucleic-acid nanostructures will play, at the same time, structural and genetic roles, the sought synergy between genetic replication, segregation, compartment growth and division will naturally emerge, making these devices the first synthetic cell implementation capable of supporting these key stages of cell replication.