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Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability

Overview of attention for article published in BMC Systems Biology, June 2016
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Title
Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability
Published in
BMC Systems Biology, June 2016
DOI 10.1186/s12918-016-0279-y
Pubmed ID
Authors

Nikolay Martyushenko, Sigurd Hagen Johansen, Cheol-Min Ghim, Eivind Almaas

Abstract

Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics. Here, we analyze the bistability properties of a general, asymmetric genetic toggle switch based on a chemical-reaction kinetic description. By making appropriate approximations, we are able to reduce the system to two coupled differential equations. Their deterministic stability analysis and stochastic numerical simulations are in excellent agreement. Drawing upon this general framework, we develop a model of an experimentally realized asymmetric bistable genetic switch based on the LacI and TetR repressors. By varying the concentrations of two synthetic inducers, doxycycline and isopropyl β-D-1-thiogalactopyranoside, we predict that it will be possible to repeatedly fine-tune the mode of operation of this genetic switch from monostable to bistable, as well as the switching rates over many orders of magnitude, in an experimental setting. Furthermore, we find that the shape and size of the bistability region is closely connected with plasmid copy number. Based on our numerical calculations of the LacI-TetR asymmetric bistable switch phase diagram, we propose a generic work-flow for developing and applying biomolecular probes: Their initial state of operation should be specified by controlling inducer concentrations, and dilution due to cellular division would turn the probes into memory devices in which information could be preserved over multiple generations. Additionally, insights from our analysis of the LacI-TetR system suggest that this particular system is readily available to be employed in this kind of probe.

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Mendeley readers

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The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 20 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 20%
Student > Master 4 20%
Student > Bachelor 3 15%
Student > Doctoral Student 2 10%
Professor 1 5%
Other 2 10%
Unknown 4 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 30%
Agricultural and Biological Sciences 4 20%
Computer Science 4 20%
Mathematics 1 5%
Engineering 1 5%
Other 0 0%
Unknown 4 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 June 2016.
All research outputs
#18,462,696
of 22,876,619 outputs
Outputs from BMC Systems Biology
#834
of 1,142 outputs
Outputs of similar age
#256,379
of 340,764 outputs
Outputs of similar age from BMC Systems Biology
#7
of 7 outputs
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So far Altmetric has tracked 1,142 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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