Abstract: Building Life-Like Systems: Synthetic Viruses & Programmable Cellular Organization
Understanding how living systems organize and function from molecular components is a central challenge across physics, biology, and engineering. I will present our collaborative projects that address this goal across scales. I’ll describe an all–cell-free framework for rapid phage genome construction, synthesis, and selection, enabling direct functional screening of engineered viruses in vitro. I will show how this can be harnessed to reconstitute complete bacteriophage lifecycle in vitro, enabling infection, genome replication, and particle assembly in synthetic cell compartments. These synthetic infection cycles allow quantitative dissection of viral dynamics and self-assembly outside host physiology. I will then discuss engineered RNA phase-separation systems that program intracellular condensates in living cells. By encoding interaction rules into RNA sequences, these systems allow rational control of mesoscale organization and offer a route to test physical principles of compartmentalization in cellular environments.
Together, these approaches illustrate how biological organization can be reconstructed, analyzed, and engineered using physically defined systems, bridging minimal synthetic platforms and living cells toward a predictive framework for designing life-like matter, opening avenues for programmable viral systems and synthetic organelles for high-throughput functional exploration, and bottom-up investigations of life’s minimal requirements.
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(2) Levrier, A. et al. Nat Commun 17, 557 (2026). doi.org/10.1038/s41467-025-67249-8;
(3) H. Guo et al (2022) Cell 185, 3823 10.1016/j.cell.2022.09.016
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