Biology subjects

Salzano, D.

Publications and source records attributed to Salzano, D..

3 recordsLinked to original sources

bioRxiv2020

Multicellular feedback control of a genetic toggle-switch in microbial consortia

We describe a multicellular approach to control a target cell population endowed with a bistable toggle-switch. The idea is to engineer a synthetic microbial consortium consisting of three different cell populations. In such a consortium, two populations, the Togglers, responding to some reference input, can induce the switch of a bistable memory mechanism in a third population, the Targets, so as to activate or deactivate some additional functionalities in the cells. Communication among the three populations is established by orthogonal quorum sensing molecules that are used to close a feedback control loop across the populations. The control design is validated via in-silico experiments in BSim, a realistic agent-based simulator of bacterial populations.Competing Interest StatementThe authors have declared no competing interest.View Full Text

synthetic biology↗

bioRxiv2020

In vivo Feedback Control of an Antithetic Molecular-Titration Motif in Escherichia coli using Microfluidics

We study both in silico and in vivo the real-time feedback control of a molecular titration motif that has been earmarked as a fundamental component of antithetic and multicellular feedback control schemes in E. coli. We show that an external feedback control strategy can successfully regulate the average fluorescence output of a bacterial cell population to a desired constant level in real-time. We also provide in silico evidence that the same strategy can be used to track a time-varying reference signal where the set-point is switched to a different value halfway through the experiment. We use the experimental data to refine and parameterize an in silico model of the motif that can be used as an error computation module in future embedded or multicellular control experiments.

synthetic biology↗

bioRxiv2019

Balancing cell populations endowed with a synthetic toggle switch via adaptive pulsatile feedback control

Controlling cells endowed with the genetic toggle switch has been suggested as a benchmark problem in synthetic biology. It has been shown that a carefully selected periodic forcing can balance a population of such cells in an undifferentiated state. The effectiveness of these control strategies, however, can be mined by the presence of stochastic perturbations and uncertainties typically observed in biological systems and is therefore not robust. Here, we propose the use of feedback control strategies to enhance robustness and performance of the balancing action by selecting in real-time both the amplitude and the duty-cycle of the inducer molecular signals affecting the toggle switch behavior. We show, via in-silico experiments and realistic agent-based simulations, the effectiveness of the proposed strategies even in presence of uncertainties and stochastic effects. In so doing, we confirm previous observations made in the literature about coherence of the population when pulsatile forcing inputs are used but, contrary to what proposed in the past, we leverage feedback control techniques to endow the balancing strategy with unprecedented robustness and stability properties. We compare via in-silico experiments different control solutions and show their advantages and limitations from an in-vivo implementation viewpoint.

synthetic biology↗