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Communication between two animals occurs when one animal transmits an information signal that causes a change in the animal that receives the information. Organisms communicate with one another in a host of different ways. Signals can be auditory, chemical, visual, tactile, or a combination of these. Communication is a critical behavioral adaptation that promotes survival, growth, and reproduction.
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A scalable peptide-GPCR language for engineering multicellular communication.

Sonja Billerbeck1, James Brisbois1, Neta Agmon2

  • 1Department of Chemistry, Columbia University, New York, New York, 10027, USA.

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Synthetic biology advances multicellular systems using a novel yeast signaling language. This scalable system, based on peptide-G-protein-coupled receptor pairs, enables complex communication networks for engineered biological communities.

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Area of Science:

  • Synthetic Biology
  • Chemical Biology
  • Systems Biology

Background:

  • Engineering multicellularity is crucial for synthetic biology, but limited scalable signaling languages hinder progress.
  • A key bottleneck is the lack of numerous, simultaneously usable communication interfaces.
  • Existing methods lack the scalability needed for complex multicellular systems.

Purpose of the Study:

  • To develop a modular, scalable intercellular signaling language for synthetic biology applications.
  • To harness natural peptide-G-protein-coupled receptor (GPCR) pairs for robust communication interfaces.
  • To enable the construction of complex multicellular systems through engineered communication.

Main Methods:

  • Genome mining to identify and assemble 32 functional fungal peptide-GPCR signaling interfaces.
  • Demonstration of two-cell communication links as building blocks for higher-order topologies.
  • Assembly of three- to six-member communication topologies and an interdependent community.

Main Results:

  • Successfully identified and characterized 32 peptide-GPCR signaling interfaces with tunable dose-response characteristics.
  • Established 56 functional two-cell communication links.
  • Assembled complex multicellular communication topologies, including a three-member interdependent community.

Conclusions:

  • A scalable, modular intercellular signaling language based on natural peptide-GPCR pairs has been established for yeast synthetic biology.
  • This language enables the construction of complex, higher-order communication networks essential for engineering multicellular systems.
  • The system is genetically tunable, requires minimal engineering, and offers significant potential for massive scalability.