Synthetic P-bodies: Coupling gene expression and ribonucleoprotein granules in synthetic cell vesicles for sensing and response

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Synthetic biologists are embarking on efforts to build synthetic cells with specific functions and desired applications such as the ability to eradicate infection-causing microbes or the ability to breakdown toxic chemicals in the environment. One basic function these synthetic cells will need is the ability to actively sense and respond to the external environment. The goal of this project is to test a synthetic compartmentalization system known as programmable bodies or P-bodies, which is designed to provide synthetic cells with the ability to sense and respond to environmental cues. In addition to the development of synthetic P-bodies, this project will allow an interdisciplinary team to train graduate and undergraduate students, to expand the intellectual and professional networks available to participants, and to design and deliver a learning module on “synthetic life ethics.”This project integrates advances in bottom-up synthetic biology and engineering of liquid-liquid phase separation of intrinsically disordered proteins, nucleic-acid binding proteins, and nucleic acids. Specifically, the goal is to develop a versatile synthetic cell platform that integrates intracellular synthetic P-bodies which dynamically respond to, and regulate, gene expression in manners analogous to natural membraneless organelles. These bodies comprise phase-separated nucleic acids and engineered fusions of intrinsically disordered proteins and ribonucleoproteins. Their dynamic and reversible formation and dissolution is mediated by chemically induced gene expression to enable chemical sensing. Molecular-level response is likewise enabled by the triggered formation and dissolution of the synthetic P-bodies to sequester or release molecular cargo. The project integrates synthetic cells into functional hybrid materials systems for the specific application of controlling formation of bacterial biofilms.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.