A scalable peptide-GPCR language for engineering multicellular communicationBillerbeck, 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 journal › Article › Academic › peer-review
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.
|Number of pages||12|
|Publication status||Published - 29-Nov-2018|
- CELL-CELL COMMUNICATION, SACCHAROMYCES-CEREVISIAE, BIOSYNTHESIS, INTERFERENCE, SYSTEMS