Noise and kinetics of LuxR positive feedback loops

Sayut, Daniel J.; Kambam, Pavan Kumar Reddy; Sun, Lianhong

doi:10.1016/j.bbrc.2007.09.057

Cited by 14 publications

(8 citation statements)

References 26 publications

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“…Stricker and coworkers [8], on the other hand, built a simple oscillator by coupling positive feedback with negative feedback. In work most closely related to the present study, Sayut and coworkers [9,10] demonstrated that a positive feedback loop could make the transcriptional activity of the quorum-sensing regulator LuxR more sensitive to autoinducer. In these regards, their design is most closely related to how positive feedback is typically employed in electronic circuits, namely to amplify the response to a signal.…”

Section: Introductionsupporting

confidence: 51%

A modular positive feedback-based gene amplifier

Nistala

Rao

et al. 2010

J Biol Eng

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BackgroundPositive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors.ResultsWe developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity.ConclusionsThe advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.

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Section: Introductionsupporting

confidence: 51%

A modular positive feedback-based gene amplifier

Nistala

Rao

et al. 2010

J Biol Eng

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“…Positive feedback loops in QS‐regulated processes are less well characterized. In V. fischeri the autoregulatory feedback seems to be dependent on LuxR and LuxI (Sayut et al ., 2007). In V. harveyi, QS‐controlled gene expression is rather complex, and the three autoinducers, HAI‐1, AI‐2 and CAI‐1, display synergistic activity.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in quorum sensing‐regulated bioluminescence of Vibrio harveyi

Anetzberger

Pirch

Jung³

2009

Molecular Microbiology

151

155

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SummaryQuorum sensing (QS) refers to the ability of bacterial populations to read out the local environment for cell density and to collectively activate gene expression. Vibrio harveyi, one of the best characterized model organisms in QS, was used to address the question how single cells behave within a QS-activated community in a homogeneous environment. Analysis of the QS-regulated bioluminescence of a wild type strain revealed that even at high cell densities only 69% of the cells of the population produced bioluminescence, 25% remained dark and 6% were dead. Moreover, light intensities greatly varied from cell to cell at high population density. Addition of autoinducer to a bright liquid culture of V. harveyi increased the percentage of luminescent cells up to 98%, suggesting that V. harveyi produces and/or keeps the autoinducers at non-saturating concentrations. In contrast, all living cells of a constitutive QS-active mutant (DluxO) produced light. We also found that QS affects biofilm formation in V. harveyi. Our data provide first evidence that a heterogeneous population produces more biofilm than a homogeneous one. It is suggested that even a QS-committed population of V. harveyi takes advantage of heterogeneity, which extends the current view of QS-regulated uniformity.

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“…To model the dynamics of the positive feedback system, we applied a model originally presented by Lewis and co-workers in 1977 [29-31]. The model demonstrates how positive feedback can lead to bistability and memory; it is presented in Equation 1.…”

Section: Modelmentioning

confidence: 99%

Hidden hysteresis – population dynamics can obscure gene network dynamics

Poisson

Bhalerao

2013

J Biol Eng

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BackgroundPositive feedback is a common motif in gene regulatory networks. It can be used in synthetic networks as an amplifier to increase the level of gene expression, as well as a nonlinear module to create bistable gene networks that display hysteresis in response to a given stimulus. Using a synthetic positive feedback-based tetracycline sensor in E. coli, we show that the population dynamics of a cell culture has a profound effect on the observed hysteretic response of a population of cells with this synthetic gene circuit.ResultsThe amount of observable hysteresis in a cell culture harboring the gene circuit depended on the initial concentration of cells within the culture. The magnitude of the hysteresis observed was inversely related to the dilution procedure used to inoculate the subcultures; the higher the dilution of the cell culture, lower was the observed hysteresis of that culture at steady state. Although the behavior of the gene circuit in individual cells did not change significantly in the different subcultures, the proportion of cells exhibiting high levels of steady-state gene expression did change.Although the interrelated kinetics of gene expression and cell growth are unpredictable at first sight, we were able to resolve the surprising dilution-dependent hysteresis as a result of two interrelated phenomena - the stochastic switching between the ON and OFF phenotypes that led to the cumulative failure of the gene circuit over time, and the nonlinear, logistic growth of the cell in the batch culture.ConclusionsThese findings reinforce the fact that population dynamics cannot be ignored in analyzing the dynamics of gene networks. Indeed population dynamics may play a significant role in the manifestation of bistability and hysteresis, and is an important consideration when designing synthetic gene circuits intended for long-term application.

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Noise and kinetics of LuxR positive feedback loops

Cited by 14 publications

References 26 publications

A modular positive feedback-based gene amplifier

A modular positive feedback-based gene amplifier

Heterogeneity in quorum sensing‐regulated bioluminescence of Vibrio harveyi

Hidden hysteresis – population dynamics can obscure gene network dynamics

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