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Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling

Das, S; Barik, D; (2023) Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling. iScience , 26 (4) , Article 106379. 10.1016/j.isci.2023.106379. Green open access

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Abstract

Summary Designing new functional motifs with unique properties is an important objective in the realm of synthetic biology. We uncover emergent properties of positive feedback loops (PFLs) under dual input signaling using pseudo potential energy-based high-throughput bifurcation analysis. We show that under dual signaling a single PFL generates a variety of noncanonical bistable switches, with one or more bistable regions, due to fusion of multiple canonical bistable switches. Regulatory signs of the dual signaling must be coherent for mutual inhibition loop and incoherent for mutual activation loop of the PFL. Occurrence probabilities show that some of the noncanonical switches, such as isola and mushroom, are highly recurrent under random parameterization. Phase diagrams of the noncanonical switches reveal that feedback strengths of the PFL control the transition from one switch to another. Our calculations decipher the design principles of noncanonical bistable switches that originate from synthetically feasible simple PFL motifs under dual signaling.

Type: Article
Title: Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2023.106379
Publisher version: https://doi.org/10.1016/j.isci.2023.106379
Language: English
Additional information: © 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Mathematical biosciences, Systems biology, Data processing in systems biology, Synthetic biology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10171235
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