A scalable peptide-GPCR language for engineering multicellular communication

Sonja Billerbeck, James Brisbois, Neta Agmon, Miguel Jimenez, Jasmine Temple, Michael Shen, Jef D. Boeke and Virginia W. Cornish ()
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Sonja Billerbeck: Columbia University
James Brisbois: Columbia University
Neta Agmon: NYU Langone Health
Miguel Jimenez: Columbia University
Jasmine Temple: NYU Langone Health
Michael Shen: NYU Langone Health
Jef D. Boeke: NYU Langone Health
Virginia W. Cornish: Columbia University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Engineering multicellularity is one of the next breakthroughs for Synthetic Biology. A key bottleneck to building multicellular systems is the lack of a scalable signaling language with a large number of interfaces that can be used simultaneously. Here, we present a modular, scalable, intercellular signaling language in yeast based on fungal mating peptide/G-protein-coupled receptor (GPCR) pairs harnessed from nature. First, through genome-mining, we assemble 32 functional peptide-GPCR signaling interfaces with a range of dose-response characteristics. Next, we demonstrate that these interfaces can be combined into two-cell communication links, which serve as assembly units for higher-order communication topologies. Finally, we show 56 functional, two-cell links, which we use to assemble three- to six-member communication topologies and a three-member interdependent community. Importantly, our peptide-GPCR language is scalable and tunable by genetic encoding, requires minimal component engineering, and should be massively scalable by further application of our genome mining pipeline or directed evolution.

Date: 2018
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DOI: 10.1038/s41467-018-07610-2

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