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15 Pág. Centro de Biotecnología y Genómica de Plantas, Cells convert electrical signals into chemical outputs to facilitate the active transport of information across larger distances. This electrical-to-chemical conversion requires a tightly regulated expression of ion channels. Alterations of ion channel expression provide landmarks of numerous pathological diseases, such as cardiac arrhythmia, epilepsy, or cancer. Although the activity of ion channels can be locally regulated by external light or chemical stimulus, it remains challenging to coordinate the expression of ion channels on extended spatial-temporal scales. Here, we engineered yeast Saccharomyces cerevisiae to read and convert chemical concentrations into a dynamic potassium channel expression. A synthetic dual-feedback circuit controls the expression of engineered potassium channels through phytohormones auxin and salicylate to produce a macroscopically coordinated pulses of the plasma membrane potential. Our study provides a compact experimental model to control electrical activity through gene expression in eukaryotic cell populations setting grounds for various cellular engineering, synthetic biology, and potential therapeutic applications., This work was supported by the Programa de Atraccion de Talento 2017 (Comunidad de Madrid, 2017-T1/BIO-5654 to KW), Severo Ochoa (SO) Programme for Centres of Excellence in R&D from the Agencia Estatal de Investigacion of Spain (grant SEV-2016-0672 (2017–2021) to KW via the CBGP). In the frame of SEV-2016-0672 funding MA received a PhD fellowship (SEV-2016-0672-18-3: PRE2018-084946). KW was supported by Programa Estatal de Generacion del Conocimiento y Forta lecimiento Cientıfico y Tecnologico del Sistema de I+D+I 2019 (PGC2018-093387-A-I00) from MICIU (to KW). UPM Plan Propio Predoctoral fellow finances MGN

10 Pág. Centro de Biotecnología y Genómica de Plantas (CBGP), The synchronization is a recurring phenomenon in neuroscience, ecology, human sciences, and biology. However, controlling synchronization in complex eukaryotic consortia on extended spatial-temporal scales remains a major challenge. Here, to address this issue we construct a minimal synthetic system that directly converts chemical signals into a coherent gene expression synchronized among eukaryotic communities through rate-dependent hysteresis. Guided by chemical rhythms, isolated colonies of yeast Saccharomyces cerevisiae oscillate in near-perfect synchrony despite the absence of intercellular coupling or intrinsic oscillations. Increased speed of chemical rhythms and incorporation of feedback in the system architecture can tune synchronization and precision of the cell responses in a growing cell collectives. This synchronization mechanism remain robust under stress in the two-strain consortia composed of toxin-sensitive and toxin-producing strains. The sensitive cells can maintain the spatial-temporal synchronization for extended periods under the rhythmic toxin dosages produced by killer cells. Our study provides a simple molecular framework for generating global coordination of eukaryotic gene expression through dynamic environment., This work was supported by the Programa de Atraccion de Talento 2017 (Comunidad de Madrid, 2017-T1/BIO-5654 to K.W.), Severo Ochoa (SO) Programme for Centres of Excellence in R&D from the Agencia Estatal de Investigacion of Spain (grant SEV-2016-0672 (2017-2021) to K.W. via the CBGP). In the frame of SEV-2016-0672 funding M.A. received a PhD fellowship (SEV-2016-0672-18-3: PRE2018-084946) and O.P. is supported with a postdoctoral contract. K.W. was supported by Programa Estatal de Generacion del Conocimiento y Fortalecimiento Cientıfico y Tecnologico del Sistema de I + D + I 2019 (PGC2018-093387-A-I00) from MICIU (to K.W.). UPM Plan Propio Predoctoral fellow finances M. G.N.

Excitable cells can convert electrical signals into chemical outputs to facilitate the active transport of information across larger distances. This electrical-to-chemical conversion requires a tightly regulated expression of ion channels. Alterations of ion channel expression provide landmarks of numerous pathological diseases, such as cardiac arrhythmia, epilepsy, or cancer. Although the activity of ion channels can be locally regulated by external light or chemical stimulus, it remains challenging to coordinate the expression of ion channels on extended spatial-temporal scales in a non-invasive manner. Here, we have engineered yeast S. cerevisiae to read and convert local chemical concentrations into a dynamic electrical field distributed across cell populations. The core mechanism encodes a chemically-excitable dual-feedback gene circuit that precisely tunes the expression domain of potassium channels, globally coordinating cyclic firing of the plasma membrane potential (PMP). We demonstrate that this mechanism leverages an engineered constitutively open bacterial potassium channel KcsA to directly couple chemical stimuli with ion flux through gene expression and it can interface with the host ion channels through the pulsatile production of toxins. Our study provides a robust synthetic transcriptional toolbox underlying the conversion of local chemical environments into spatiotemporally organized electrical impulses for various cellular engineering, synthetic biology, and potential therapeutic applications.