A scalable peptide-GPCR language for engineering multicellular communication

Billerbeck, S., Brisbois, J., Agmon, N., Jimenez, M., Temple, J., Shen, M., Boeke, J. D. & Cornish, V. W., 29-Nov-2018, In : Nature Communications. 9, 12 p., 5057.

Research output: Contribution to journalArticleAcademicpeer-review

  • Sonja Billerbeck
  • James Brisbois
  • Neta Agmon
  • Miguel Jimenez
  • Jasmine Temple
  • Michael Shen
  • Jef D. Boeke
  • Virginia W. Cornish

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.

Original languageEnglish
Article number5057
Number of pages12
JournalNature Communications
Publication statusPublished - 29-Nov-2018
Externally publishedYes



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