EAGER: Actuation of Synthetic Cells Via Proto-Flagellar Motors

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This is a project that focuses on the development of functioning molecular motors for micron-scale synthetic cells, demonstrating mechanisms for motility in (synthetic) cellular systems. Recent advances in the fields of synthetic biology and molecular sciences have substantially advanced the ability to produce genetically-programmed synthetic cells and multicellular machines from molecular components. These efforts provide techniques for the bottom-up construction of cell-like systems that can provide scientists with new insights into how natural cells work, harness the power of biology to create nanoscale, biomolecular machines, and provide an exciting pathway for exploration of the Rules of Life. This project considers the ‘actuation’ subsystem of a synthetic cell, with the goal of allowing expression of membrane-integrated actuation complexes that can serve as a starting point to modulate the motility of the cell. The project engages undergraduate students from the Summer Undergraduate Research Fellowship program at California Institute of Technology and establishes collaborations between the US Build-A-Cell consortium and Imperial College, London, that includes personnel exchanges to build stronger international ties.To demonstrate the ability to express actuation complexes capable of modulating motility, this project (i) creates and optimizes vesicles with reconstituted transmembrane complexes (proto-flagella) that can eventually drive motility and (ii) engineers new vesicle systems that rely on TX-TL for the synthesis of the soluble and membrane proteins needed for motility. The project team redefines the state of the art by driving a step change in the type and complexity of behavioral modules that can be introduced into synthetic cells. Reconstituting membrane proteins provides new insights into the biological processes that underlie mechanisms for motility in microorganisms. In conjunction, the project develops generic methodologies for achieving in vesicle genetic control of membrane proteins, using proto-flagella as a test case.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.