RoL:EAGER: DESYN-C3. Bottom-up Synthetic Cells Capable of Darwinism, the Archetypal Trait of Life

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With this award, the Chemistry of Life Processes (CLP) Program in the Division of Chemistry is funding work under the direction of Dr. Steven Benner from the Foundation for Applied Molecular Evolution to create stable artificial cells that may be used in biotechnology, especially in directed evolution. A "bottom-up" program to create artificial cells avoids the need to manage the complexity of modern living cells, a management necessary in "top-down" approaches to minimal cells. However, it requires in turn a cellular architecture simpler than the "water-oil-water" architecture of natural cells. The research focuses on gaining control over phase separation that creates a cell structure with water inside the cell and oil outside through control over surfactants, which are small molecules that have a side that "prefers" to orient toward water and another side that prefers to orient toward the oil. These molecules determine the properties of boundaries and interfaces between the water and oil and in turn can be used in the reproducible preparation of artificial cells that are uniform in size. Such control has been sought for 20 years now and the availability of "off-the-shelf" surfactants that make control possible would boost the efforts to create an artificial cell using a bottom up approach. The research focuses on the incorporation into the artificial cell of genetic systems that themselves can evolve, ultimately to influence the properties of the cells in a way that alters cellular fitness.This project will create synthetic pipelines to make surfactants that give reproducible control over the physical properties of water-oil emulsions from which stable, robust and uniformly sized nanodroplets (synthetic cells) in oil can be prepared. We will develop surfactants that do not denature the enzymes, genes, and other biologics that reside within the cells. The artificial cell architecture involves just two phases, an external lipid phase and internal water phase. Systems that allow the delivery of water and other small molecules to the cell will be integrated in the synthetic cells. The research will then aim to create a mechanism by which the synthetic cells can change their external traits in response to molecular evolution processes that takes plan in the cell.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.