How to tell bistable cells in which state they should be? On modeling of population fraction control using light.View all posters
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 . Also QS was used to synchronize oscillators in  and to tune two-step bistable circuits inducing phenotypic diversification in . 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 , which can be found as part BBa_R0061 from the Registry of Standard Biological Parts. We rely on the CcaS/CcaR TCSs system , 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:  A. Tamsir, et al. Robust multicellular computing using genetically encoded NOR gates and chemical wires, Nature (2010).  T. Danino, et al. A Synchronized Quorum of Genetic Clocks, Nature (2010).  R. Sekine, et al. Tunable synthetic phenotypic diversification on Waddington’s landscape through autonomous signaling. PNAS (2011).  K. A. Egland, et al. Conversion of the Vibrio fischeri transcriptional activator, LuxR, to a re-pressor, Journal of Bacteriology (2000).  J.J. Tabor, et al. Multichromatic control of gene expression in Escherichia coli. J Molecular Biology (2011).