How to tell bistable cells in which state they should be? On modeling of population fraction control using light.

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Alejandro Vignoni, Gabriel Bosque, Jeffrey J. Tabor, Jess Pic

Automatic Control and Industrial Computing Institute, Spain

Quorum Sensing mechanisms have been on the table in the last few years. Auto-inducer mole-cules were used as “chemical wires” to obtain in vivo logic circuits [1]. Also QS was used to synchronize oscillators in [2] and to tune two-step bistable circuits inducing phenotypic diversification in [3]. In this contribution, we use QS to indirectly drive a population of bistable cells to a desired state in a robust way, by using a second mediating population of regulatory cells. On the one hand, the bistable cells carry a genetic circuit containing the LuxI-LuxR-AHL system along with the LuxR-AHL activated promoter, thus implementing a positive feedback loop in a one-step circuit. Regulatory cells, on the other hand, have a regulated circuit that contains a negative feedback loop based also on the LuxI-LuxR-AHL system, but using an engineered LuxR-AHL repressible promoter [4], which can be found as part BBa_R0061 from the Registry of Standard Biological Parts. We rely on the CcaS/CcaR TCSs system [5], and use light as a control knob to drive the regulatory cells to a desired expression level of LuxI. This, in turn leads to set the appropriate level of the auto-inducer signal to broadcast to the bistable cells. This control of the population-ratio of bistable cells in each of both states has broad applications in synthetic biology. References: [1] A. Tamsir, et al. Robust multicellular computing using genetically encoded NOR gates and chemical wires, Nature (2010). [2] T. Danino, et al. A Synchronized Quorum of Genetic Clocks, Nature (2010). [3] R. Sekine, et al. Tunable synthetic phenotypic diversification on Waddington’s landscape through autonomous signaling. PNAS (2011). [4] K. A. Egland, et al. Conversion of the Vibrio fischeri transcriptional activator, LuxR, to a re-pressor, Journal of Bacteriology (2000). [5] J.J. Tabor, et al. Multichromatic control of gene expression in Escherichia coli. J Molecular Biology (2011).