The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two artificial cell-cell communication systems in yeast. We integrated Arabidopsis thaliana signal synthesis and receptor components with yeast endogenous protein phosphorylation elements and new response promoters. In the first system, engineered yeast 'sender' cells synthesize the plant hormone cytokinin, which diffuses into the environment and activates a hybrid exogenous/endogenous phosphorylation signaling pathway in nearby engineered yeast 'receiver' cells. For the second system, the sender network was integrated into the receivers under positive-feedback regulation, resulting in population density–dependent gene expression (that is, quorum sensing). The combined experimental work and mathematical modeling of the systems presented here can benefit various biotechnology applications for yeast and higher level eukaryotes, including fermentation processes, biomaterial fabrication and tissue engineering.
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We thank Y. Gerchman, D. Karig, S. Basu and S. Subramanian for helpful discussions. We also thank T. Kakimoto and S. Avery for the gift of yeast strain and plasmids and R. Kerstetter for A. thaliana genomic DNA extract. This work was supported by a Burroughs Wellcome Fund fellowship.
The authors declare no competing financial interests.
Simulated cytokinin receiver behavior. (PDF 74 kb)
Simulated quorum sensing behaviors. (PDF 80 kb)
Definitions. (PDF 42 kb)
Chemical Reactions. (PDF 536 kb)
Differential Equations. (PDF 19 kb)
Kinetic Constants (units in μM and minute). (PDF 80 kb)
Plasmids used in this work. (PDF 45 kb)
Yeast strains used in this study. (PDF 32 kb)
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