RoL: RAISE: DESYN-C3: Engineering multi-compartmentalised synthetic minimal cells

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This project aims to create tools for construction of functional artificial cells by building on new insight into how organelles are generated and maintained in natural cells. At a glance, eukaryotic organelles could be described as small intracellular compartments delineated from the rest of the cell content by a membrane made up of molecules called lipids. The organelles are critical for the life of the cell and in turn their formation depends on the self-assembly of the lipids into membranes and on the coexistence of different liquid phases. Consequently the lipid self-assembly and the coexistence of liquid-liquid phases are the object of on-going investigations. In contrast, the interactions between these two processes are largely unexplored. With this award, the Chemistry of Life Processes Program in the Division of Chemistry and the Cellular and Biochemical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems are funding Dr. Christine Keating from Penn State University and Dr. Kate Adamala from the University of Minnesota to investigate how the two main types of intracellular organizational processes interact with each other. This interdisciplinary research generates a stepping stone on the path to the construction of artificial organelles and in the long term of artificial cells. The research also represents an opportunity for the scientific training and professional development of graduate students, undergraduates, and K-12 teachers. This research project explores cytoplasm-mimicking systems in which lipids and phase-separating proteins are enzymatically produced by cell-free transcription/translation. In vitro lipid biosynthesis pathways are developed for in situ lipid generation in model cytoplasm. The self-assembly of these lipids in the presence of model membraneless organelles is characterized by optical and electron microscopies as well as by permeability measurements. This project seeks to engineer artificial cells capable of producing functional synthetic lipid membranes and inducible stress granules. The findings advance the understanding of physical mechanisms for organellogenesis, and how local lipid production and media compartmentalization impact these mechanisms.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.