Entrainment and Control of Bacterial Populations: An <i>in Silico</i> Study over a Spatially Extended Agent Based Model

Mina, Petros; Tsaneva-Atanasova, Krasimira; Bernardo, Mario di

doi:10.1021/acssynbio.5b00243

Cited by 6 publications

(3 citation statements)

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“…With a view toward the in vivo implementation, we next assessed via agent-based simulations the performance of both control strategies. To this aim we conducted in silico experiments with BSim 2.0, an advanced agent-based simulator of bacterial populations , that is able to replicate realistic phenomena such as cell growth, spatial diffusion, variability in cell geometry, and flush-out of the cells from the microfluidic chamber (see Methods for further details). Figure shows the results of the agent-based simulations confirming the effectiveness and viability of the strategies for in vivo experiments.…”

Section: Resultsmentioning

confidence: 99%

“…Agent-based simulations were implemented in BSim 2.0, an advanced bacteria simulator developed in Java. , Inspired by the so-called mother machine in microfluidics, we designed a 1 × 30 × 1 μm rectangular chamber that hosts a single layer cell population where cells are lined up. The chamber is open on the top (short side), from where the inducers diffuses and cells are flushed out due to their own growth and medium flow.…”

Section: Methodsmentioning

confidence: 99%

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Balancing Cell Populations Endowed with a Synthetic Toggle Switch via Adaptive Pulsatile Feedback Control

et al. 2020

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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 realtime 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 . CC-BY-NC-ND 4.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Balancing Cell Populations Endowed with a Synthetic Toggle Switch via Adaptive Pulsatile Feedback Control

et al. 2020

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“…There are known advantages of in silico modelling the action of therapeutic agents on known diseases through agent-based modelling 74 . However, the literature evidenced some intrinsic limitations on the choice of parameters, like the size of investigated populations 75 , while major problems are related to model validation 75,76 , also requiring to supplement the models with adequate formal ontologies 77 . Thanks to its abstract nature, stock-flow description can be used in a wide range of different fields, realizing the conceptual bridge that connects the language of biological systems to that of ecology.…”

Section: Discussionmentioning

confidence: 99%

Energy dynamics for systemic configurations of virus-host co-evolution

Romano

Casazza

Gonella

2020

Preprint

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ArticlePositive single-stranded RNA ((+)ssRNA) viruses, including picornaviruses, flaviviruses, togaviridae and human coronaviruses (h-CoVs) 1-4 cause multiple outbreaks, for which tailored antiviral strategies are still missing [5][6][7] . (+)ssRNA viruses package their genomes as messenger sense, single stranded RNA and replicate those genomes solely through RNA intermediates in the cytosol of the host cells 8 . RNA-dependent RNA polymerases lack co-and post-replicative fidelity-enhancing pathways, and final RNA genome copies incorporate mutations at a much higher rate than that observed for DNA genomes 9,10 providing the viral quasispecies a higher probability to evolve and adapt to new environments and challenges during infection 11,12 . The diversity is essential for both viral fitness and pathogenesis, due to the complex relationship between virus replication, host cells and immune system, since almost +RNA viruses can delay antiviral innate immune response 13 in multiple ways [14][15][16][17][18][19][20] . Host immunogenetic factors can be sensitive to a variation in the viral load, conveying to a defective response of the innate immunity that could explain the variable clinical course of infection 20,21 . Among (+)ssRNA viruses, h-CoVs have unusually large genomes (∼30 kb) associated with low mutation rates 20,22 . Three novel h-CoVs are etiological agents of serious viral interstitial pneumonia 23 . They include the severe acute respiratory syndrome, first described in Guandong province in China in 2002 24 , the Middle East respiratory syndrome (caused by MERS-CoV), emerged in June 2012 in Saudi Arabia and Qatar 25 , and the SARS-CoV-2, emerged in China in January 2020, cause of the largest outbreak in the modern history 23 .Recent studies confirmed the complexity of viral dynamics, whose fitness is improved by the complex interactions with the host proteins 26,27 as previously described in modelling the virus-host interactions at sub-cell and cell levels 6,28-31 . However, models that address a specific aspect of the virus-host interaction do not capture the wide range of intertwined spatial and temporal (hours to days) dynamic scales 32 , that are related to the interaction of different concurrent hierarchical levels.All these factors address the need for a description able to connect all the levels at which the infection proceeds within a single cell, from the recruitment of RNA-synthesis factory to the final host cell damage. Several drugs, such as chloroquine 33,34 , hydroxychloroquine, ribavirin, lopinavir-ritonavir 35 , were used in patients with SARS [33][34][35] or MERS 7 and are currently under investigation, alone or in combination, to control the COVID-19 infection [36][37][38][39][40][41][42][43][44][45][46][47] . However, there is an urgent need of a new class of compounds, other than nucleotides mimetics, due their low-fidelity viral RNA polymerase 48 to combine with host factor targeting agents, recently identified to lead to a therapeutic regimen to treat COVID-19 6 .We show that, b...

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