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A scalable peptide-GPCR language for engineering multicellular communication

Author

Listed:
  • Sonja Billerbeck

    (Columbia University)

  • James Brisbois

    (Columbia University)

  • Neta Agmon

    (NYU Langone Health)

  • Miguel Jimenez

    (Columbia University
    The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

  • Jasmine Temple

    (NYU Langone Health)

  • Michael Shen

    (NYU Langone Health)

  • Jef D. Boeke

    (NYU Langone Health)

  • Virginia W. Cornish

    (Columbia University
    Columbia University)

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.

Suggested Citation

  • Sonja Billerbeck & James Brisbois & Neta Agmon & Miguel Jimenez & Jasmine Temple & Michael Shen & Jef D. Boeke & Virginia W. Cornish, 2018. "A scalable peptide-GPCR language for engineering multicellular communication," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07610-2
    DOI: 10.1038/s41467-018-07610-2
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    Cited by:

    1. Emil D. Jensen & Marcus Deichmann & Xin Ma & Rikke U. Vilandt & Giovanni Schiesaro & Marie B. Rojek & Bettina Lengger & Line Eliasson & Justin M. Vento & Deniz Durmusoglu & Sandie P. Hovmand & Ibrahim, 2022. "Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Alice Boo & Tyler Toth & Qiguo Yu & Alexander Pfotenhauer & Brandon D. Fields & Scott C. Lenaghan & C. Neal Stewart & Christopher A. Voigt, 2024. "Synthetic microbe-to-plant communication channels," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. John P. Marken & Richard M. Murray, 2023. "Addressable and adaptable intercellular communication via DNA messaging," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Karel Miettinen & Nattawat Leelahakorn & Aldo Almeida & Yong Zhao & Lukas R. Hansen & Iben E. Nikolajsen & Jens B. Andersen & Michael Givskov & Dan Staerk & Søren Bak & Sotirios C. Kampranis, 2022. "A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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