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

Author(s):  
Davide Fiore ◽  
Davide Salzano ◽  
Enric Cristòbal-Cóppulo ◽  
Josep M. Olm ◽  
Mario di Bernardo

AbstractWe 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.

2021 ◽  
Author(s):  
Davide Salzano ◽  
Davide Fiore ◽  
Mario di Bernardo

We address the problem of regulating and keeping at a desired balance the relative numbers between cells exhibiting a different phenotype within a monostrain microbial consortium. We propose a strategy based on the use of external control inputs, assuming each cell in the community is endowed with a reversible, bistable memory mechanism. Specifically, we provide a general analytical framework to guide the design of external feedback control strategies aimed at balancing the ratio between cells whose memory is stabilized at either one of two equilibria associated to different cell phenotypes. We demonstrate the stability and robustness properties of the control laws proposed and validate them in silico implementing the memory element via a genetic toggle-switch. The proposed control framework may be used to allow long term coexistence of different populations, with both industrial and biotechnological applications. Examples include consortia where each population produces a compound of interest or where one population supports the growth of the other which has the role of producing a desired molecule. As a representative example we consider the realistic agent-based implementation of our control strategy to enable cooperative bioproduction in microbial consortia.


2021 ◽  
Vol 5 (1) ◽  
pp. 151-156 ◽  
Author(s):  
Davide Fiore ◽  
Davide Salzano ◽  
Enric Cristobal-Coppulo ◽  
Josep M. Olm ◽  
Mario di Bernardo

2019 ◽  
Author(s):  
A. Guarino ◽  
D. Fiore ◽  
D. Salzano ◽  
M. di Bernardo

AbstractControlling 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.


2021 ◽  
Author(s):  
Qinggeer BORJIGIN ◽  
Bizhou ZHANG ◽  
Xiaofang Yu ◽  
Julin Gao ◽  
Xin ZHANG ◽  
...  

Abstract A lignocellulolytic microbial consortium holds promise for the in situ biodegradation of crop straw and the comprehensive and effective utilization of agricultural waste. In this study, we applied metagenomics technology to comprehensively explore the metabolic functional potential and taxonomic diversity of the microbial consortia CS (cultured on corn stover) and FP (cultured on filter paper).Analyses of the metagenomics taxonomic affiliation data showed considerable differences in the taxonomic composition and functional profile of the microbial consortia CS and FP. The microbial consortia CS primarily contained members from the genera Pseudomonas, Stenotrophomonas, Achromobacter, Dysgonomonas, Flavobacterium and Sphingobacterium, as well as Cellvibrio, Azospirillum, Pseudomonas, Dysgonomonas and Cellulomonas in FP. The COG and KEGG annotation analyses revealed considerable levels of diversity. Further analysis determined that the CS consortium had an increase in the acid and ester metabolism pathways, while carbohydrate metabolism was enriched in the FP consortium. Furthermore, a comparison against the CAZy database showed that the microbial consortia CS and FP contain a rich diversity of lignocellulose degrading families, in which GH5, GH6, GH9, GH10, GH11, GH26, GH42, and GH43 were enriched in the FP consortium, and GH44, GH28, GH2, and GH29 increased in the CS consortium. The degradative mechanism of lignocellulose metabolism by the two microbial consortia is similar, but the annotation of quantity of genes indicated that they are diverse and vary greatly. The lignocellulolytic microbial consortia cultured under different carbon conditions (CS and FP) differed substantially in their composition of the microbial community at the genus level. The changes in functional diversity were accompanied with variation in the composition of microorganisms, many of which are related to the degradation of lignocellulolytic materials. The genera Pseudomonas, Dysgonomonas and Sphingobacterium in CS and the genera Cellvibrio and Pseudomonas in FP exhibited a much wider distribution of lignocellulose degradative ability.


2021 ◽  
Vol 10 (1) ◽  
pp. 39
Author(s):  
Xinhua Qi ◽  
Wenlong Yan ◽  
Zhibei Cao ◽  
Mingzhu Ding ◽  
Yingjin Yuan

Polyethylene terephthalate (PET) is a widely used plastic that is polymerized by terephthalic acid (TPA) and ethylene glycol (EG). In recent years, PET biodegradation and bioconversion have become important in solving environmental plastic pollution. More and more PET hydrolases have been discovered and modified, which mainly act on and degrade the ester bond of PET. The monomers, TPA and EG, can be further utilized by microorganisms, entering the tricarboxylic acid cycle (TCA cycle) or being converted into high value chemicals, and finally realizing the biodegradation and bioconversion of PET. Based on synthetic biology and metabolic engineering strategies, this review summarizes the current advances in the modified PET hydrolases, engineered microbial chassis in degrading PET, bioconversion pathways of PET monomers, and artificial microbial consortia in PET biodegradation and bioconversion. Artificial microbial consortium provides novel ideas for the biodegradation and bioconversion of PET or other complex polymers. It is helpful to realize the one-step bioconversion of PET into high value chemicals.


2020 ◽  
Vol 9 (4) ◽  
pp. 793-803 ◽  
Author(s):  
Agostino Guarino ◽  
Davide Fiore ◽  
Davide Salzano ◽  
Mario di Bernardo

2014 ◽  
Vol 67 (5) ◽  
Author(s):  
Auwalu M. Abdullahi ◽  
Z. Mohamed ◽  
Marwan Nafea M.

This paper presents resonant control of a single-link flexible manipulator based on the resonant modes frequencies of the system. A flexible manipulator system is a single-input multi-output (SIMO) system with motor torque as an input and hub angle and the tip deflection as outputs. The previous system which is modeled using the finite element method is considered, and the resonant modes of the system are determined. Two negative feedback controllers are used to control the system. The inner feedback control loop designed using the resonant frequencies adds damping to the system and suppress the vibration effect around the hub angle. For the outer feedback control loop, a proportional integral controller is designed to achieve a zero steady state error so that a precise tip positioning can be achieved. Simulation results are presented and discussed to show the effectiveness of the resonant control scheme. 


Minerals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 856
Author(s):  
Bingxu Dong ◽  
Yan Jia ◽  
Qiaoyi Tan ◽  
Heyun Sun ◽  
Renman Ruan

The function of microbial contact leaching to pyrite oxidation was investigated by analyzing the differences of residue morphologies, leaching rates, surface products, and microbial consortia under different conditions in this study. This was achieved by novel equipment that can control the redox potential of the solution and isolate pyrite from microbial contact oxidation. The morphology of residues showed that the corrosions were a little bit severer in the presence of attached microbes under 750 mV and 850 mV (vs. SHE). At 650 mV, the oxidation of pyrite was undetectable even in the presence of attached microbes. The pyrite dissolution rate was higher with attached microbes than that without attached microbes at 750 mV and 850 mV. The elemental sulfur on the surface of pyrite residues with sessile microorganisms was much less than that without attached microbes at 750 mV and 850 mV, showing that sessile acidophiles may accelerate pyrite leaching by reducing the elemental sulfur inhibition. Many more sulfur-oxidizers were found in the sessile microbial consortium which also supported the idea. The results suggest that the microbial “contact leaching” to pyrite oxidation is limited and relies on the elimination of elemental sulfur passivation by attached sulfur-oxidizing microbes rather than the contact oxidation by EPS-Fe.


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