Building biological memory by linking positive feedback loops

Chang, Dong Eun; Leung, Shelly; Atkinson, Mariette R.; Reifler, Aaron N.; Forger, Daniel B.; Ninfa, Alexander J.

doi:10.1073/pnas.0908314107

Cited by 79 publications

(78 citation statements)

References 31 publications

(55 reference statements)

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“…Positive feedback systems have been widely used in digital electronics to engineer oscillators, switches and hysteresis where the system output can take either of two stable values, and these are each kept unless a sufficiently large input stimulus is applied [51]. A detailed discussion of positive feedback is beyond the scope of this review and can be found elsewhere [46,[52][53][54][55].…”

Section: Feed-forward and Positive Feedback Systemsmentioning

confidence: 99%

Control theory meets synthetic biology

Vecchio

Qian

2016

J. R. Soc. Interface.

236

191

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The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology.

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Section: Feed-forward and Positive Feedback Systemsmentioning

confidence: 99%

Control theory meets synthetic biology

Vecchio

Qian

2016

J. R. Soc. Interface.

236

191

View full text Add to dashboard Cite

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“…Such a system will not respond gradually according to the intensity of a stimulus but will have an all or none response (77). Since the expression level depends upon its previous state, this kind of system is often linked to the notion of memory (77,78). It has been proposed that bistable systems are at the origin of the decision for cell differentiation (79).…”

Section: Attenuation Of Fluctuationsmentioning

confidence: 99%

DNA Looping in Prokaryotes: Experimental and Theoretical Approaches

Cournac

Plumbridge

2013

Journal of Bacteriology

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bTranscriptional regulation is at the heart of biological functions such as adaptation to a changing environment or to new carbon sources. One of the mechanisms which has been found to modulate transcription, either positively (activation) or negatively (repression), involves the formation of DNA loops. A DNA loop occurs when a protein or a complex of proteins simultaneously binds to two different sites on DNA with looping out of the intervening DNA. This simple mechanism is central to the regulation of several operons in the genome of the bacterium Escherichia coli, like the lac operon, one of the paradigms of genetic regulation. The aim of this review is to gather and discuss concepts and ideas from experimental biology and theoretical physics concerning DNA looping in genetic regulation. We first describe experimental techniques designed to show the formation of a DNA loop. We then present the benefits that can or could be derived from a mechanism involving DNA looping. Some of these are already experimentally proven, but others are theoretical predictions and merit experimental investigation. Then, we try to identify other genetic systems that could be regulated by a DNA looping mechanism in the genome of Escherichia coli. We found many operons that, according to our set of criteria, have a good chance to be regulated with a DNA loop. Finally, we discuss the proposition recently made by both biologists and physicists that this mechanism could also act at the genomic scale and play a crucial role in the spatial organization of genomes. Different levels of DNA organization exist within bacterial chromosomes. In the case of Escherichia coli, the genome has been shown to be organized, on the largest scale, in four individual macrodomains (Ter, Ori, Right, and Left) and two less-structured regions (1) that have a precise localization within the cell throughout the cell cycle and are associated with specific binding proteins (2). Large-scale DNA loops have been visualized by nucleoidspreading techniques and are thought to be stabilized by membrane and/or RNA components (3, 4). Then, at the scale of 10 kb, there are topological domains formed by supercoiled structures (5, 6) whose barriers are not placed stably at fixed sites but instead are randomly distributed (7). These intermediate loops can be stabilized with nucleoid-associated proteins like H-NS (8). Finally, there are smaller loops of a few hundred base pairs made by specific transcription factors that have a direct impact on transcription. Although loops of different sizes can have functional consequences for genomic organization and genetic regulation, it is the last category that we focus on in this review.A first hint that a transcription factor can bind simultaneously to two sites derived from the work of Kania and Müller-Hill in 1977 (9). However, the first experimental demonstration and clear proposal for the existence of a DNA loop affecting gene regulation was in 1984, by the team of Robert Schleif (10), working on the regulatory region of the ara...

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“…First, the CusSR TCS responds to lower concentrations of environmental copper [3]. At standard assay condition in the laboratory, the response of modified CusSR TCS network to Cu 2?…”

Section: Discussionmentioning

confidence: 99%

Modification of CusSR bacterial two-component systems by the introduction of an inducible positive feedback loop

Ravikumar

Pham

Lee³

et al. 2012

Journal of Industrial Microbiology and Biotechnology

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The CusSR two-component system (TCS) is a copper-sensing apparatus of E. coli that is responsible for regulating the copper-related homeostatic system. The dynamic characteristics of the CusSR network were modified by the introduction of a positive feedback loop. To construct the feedback loop, the CusR, which is activated by the cusC promoter, was cloned downstream of the cusC promoter and reporter protein. The feedback loop system, once activated by environmental copper, triggers the activation of the cusC promoter, which results in the amplification of a reporter protein and CusR expression. The threshold copper concentration for the activation of the modified CusSR TCS network was lowered from 2,476.5 μg/l to 247.7 μg/l, which indicates a tenfold increase in sensitivity. The intensity of the output signal was increased twofold, and was maintained for 16 h. The strategy proposed in this study can also be applied to modify the dynamic characteristics of other TCSs.

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Building biological memory by linking positive feedback loops

Cited by 79 publications

References 31 publications

Control theory meets synthetic biology

Control theory meets synthetic biology

DNA Looping in Prokaryotes: Experimental and Theoretical Approaches

Modification of CusSR bacterial two-component systems by the introduction of an inducible positive feedback loop

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