Collaborative Research: Toward lifelike synthetic cells via engineered control of DNA replication

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The ability of cells to reliably replicate and maintain genomic information is a key facet of life. Recapitulating these mechanisms is a critical step towards the development of autonomous synthetic cells that exhibit self-replication and stable propagation of their genetic information. To that end, this project creates a new synthetic mechanism for DNA replication control in synthetic cells that will open the door for new applications in biomedicine and biotechnology. This project carries out an integrated social science investigation into the current regulatory framework surrounding engineered synthetic cell technologies. This project also provides educational and technical training aimed at increasing the number and diversity of undergraduates and graduates pursuing careers in synthetic cell research. Public outreach is carried out in conjunction with local partners to increase public awareness of synthetic cell technologies. Natural cells have evolved sophisticated mechanisms to control DNA replication, to prevent the loss of critical genes while simultaneously preventing runaway replication. Analogous replication control mechanisms will be required for synthetic cells. While natural genome replication control systems are complex, plasmids provide a simple yet powerful and modular system for building synthetic replication control systems and modular genomes for synthetic cells. This project addresses the broad challenge of engineering DNA replication control mechanisms for synthetic cell systems. RNA engineering techniques are used to create modular and programmable synthetic plasmid replication control systems that function in both cells and cell-like systems. This project also studies how DNA replication can be utilized for novel biosensing applications. Biocontainment applications are investigated through an integrated social science investigation.This award is co-funded by the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences and the Cellular and Biochemical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.