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

自主复制是生物细胞生命的标志，在自下而上构建的系统中概括它代表了合成细胞科学的核心目标。过去自下而上构建自我复制的合成系统的尝试要么证明了遗传信息的复制，要么证明了细胞样隔室的生长和分裂，但在现存生命形式中整合这些关键过程的能力仍然缺乏。通过这个项目，我们将核酸纳米技术的工具包与分子生物学和生物物理学的原理相结合，解决了这一瓶颈。合成细胞将从DNA模板（“基因组”）转录的RNA构建块形成和生长。分裂和基因组分离将由相分离产生，而基因组复制（扩增）将由逆转录支撑。由于核酸纳米结构将同时发挥结构和遗传作用，因此在遗传复制、分离、室生长和分裂之间寻求的协同作用将自然出现，使这些装置成为第一个能够支持细胞复制这些关键阶段的合成细胞实现。

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.