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Modular, robust and extendible multicellular circuit design in yeast

View ORCID ProfileAlberto Carignano, Dai Hua Chen, Cannon Mallory, View ORCID ProfileClay Wright, View ORCID ProfileGeorg Seelig, View ORCID ProfileEric Klavins
doi: https://doi.org/10.1101/2021.10.13.464175
Alberto Carignano
1Department of Electrical & Computer Engineering, University of Washington
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Dai Hua Chen
1Department of Electrical & Computer Engineering, University of Washington
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Cannon Mallory
1Department of Electrical & Computer Engineering, University of Washington
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Clay Wright
3Department of Biological Systems Engineering, Virginia Tech
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Georg Seelig
1Department of Electrical & Computer Engineering, University of Washington
2Paul G. Allen School of Computer Science & Engineering, University of Washington
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  • For correspondence: gseelig@uw.edu klavins@uw.edu
Eric Klavins
1Department of Electrical & Computer Engineering, University of Washington
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  • For correspondence: gseelig@uw.edu klavins@uw.edu
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Abstract

Division of labor between cells is ubiquitous in biology but the use of multi-cellular consortia for engineering applications is only beginning to be explored. A significant advantage of multi-cellular circuits is their potential to be modular with respect to composition but this claim has not yet been extensively tested using experiments and quantitative modeling. Here, we construct a library of 24 yeast strains capable of sending, receiving or responding to three molecular signals, characterize them experimentally and build quantitative models of their input-output relationships. We then compose these strains into two- and three-strain cascades as well a four-strain bistable switch and show that experimentally measured consortia dynamics can be predicted from the models of the constituent parts. To further explore the achievable range of behaviors, we perform a fully automated computational search over all two-, three- and four-strain consortia to identify combinations that realize target behaviors including logic gates, band-pass filters and time pulses. Strain combinations that are predicted to map onto a target behavior are further computationally optimized and then experimentally tested. Experiments closely track computational predictions. The high reliability of these model descriptions further strengthens the feasibility and highlights the potential for distributed computing in synthetic biology.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/Alby86/MulticellularYeast.git

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 14, 2021.
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Modular, robust and extendible multicellular circuit design in yeast
Alberto Carignano, Dai Hua Chen, Cannon Mallory, Clay Wright, Georg Seelig, Eric Klavins
bioRxiv 2021.10.13.464175; doi: https://doi.org/10.1101/2021.10.13.464175
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Modular, robust and extendible multicellular circuit design in yeast
Alberto Carignano, Dai Hua Chen, Cannon Mallory, Clay Wright, Georg Seelig, Eric Klavins
bioRxiv 2021.10.13.464175; doi: https://doi.org/10.1101/2021.10.13.464175

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