bioRxiv (Cold Spring Harbor Laboratory) · 2019 · 13 citations · 20 references
Life SciencesBioengineeringMicrobiologyMicrobial EcologyMicrobial PhysiologySynthetic BiologyGenetic Circuit DesignMicrobial Consortia EngineeringMicrobial Synthetic BiologySynthetic Biology Circuit ModelingSynthetic Biology For MicrobesSynthetic Gene CircuitsCircuit StabilityCommensal MicrobiotaGenetic Circuit ControlInducible Circuit DesignPopulation Density DependenceRobustness Of Gene CircuitsSynthetic Biology CircuitsSynthetic Gene Circuit Design
Abstract As studies continue to demonstrate how our health is related to the status of our various commensal microbiomes, synthetic biologists are developing tools and approaches to control these microbiomes and stabilize healthy states or remediate unhealthy ones. Building on previous work to control bacterial communities, we have constructed a synthetic two-member bacterial consortium engineered to reach population density and composition steady states set by inducer inputs. We detail a screening strategy to search functional parameter space in this high-complexity genetic circuit as well as initial testing of a functional two-member circuit. We demonstrate non-independent changes in total population density and composition steady states with a limited set of varying inducer concentrations. After a dilution to perturb the system from its steady state, density and composition steady states are not regained. Modeling and simulation suggest a need for increased degradation of intercellular signals to improve circuit performance. Future experiments will implement increased signal degradation and investigate the robustness of control of each characteristic to perturbations from steady states.
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