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Functional Resilience of Mutually Repressing Motifs Embedded in Larger Networks

Harlapur, P and Duddu, AS and Hari, K and Kulkarni, P and Jolly, MK (2022) Functional Resilience of Mutually Repressing Motifs Embedded in Larger Networks. In: Biomolecules, 12 (12).

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Official URL: https://doi.org/10.3390/biom12121842


Elucidating the design principles of regulatory networks driving cellular decision-making has important implications for understanding cell differentiation and guiding the design of synthetic circuits. Mutually repressing feedback loops between ‘master regulators’ of cell fates can exhibit multistable dynamics enabling “single-positive” phenotypes: (high A, low B) and (low A, high B) for a toggle switch, and (high A, low B, low C), (low A, high B, low C) and (low A, low B, high C) for a toggle triad. However, the dynamics of these two motifs have been interrogated in isolation in silico, but in vitro and in vivo, they often operate while embedded in larger regulatory networks. Here, we embed these motifs in complex larger networks of varying sizes and connectivity to identify hallmarks under which these motifs maintain their canonical dynamical behavior. We show that an increased number of incoming edges onto a motif leads to a decay in their canonical stand-alone behaviors. We also show that this decay can be exacerbated by adding self-inhibition but not self-activation loops on the ‘master regulators’. These observations offer insights into the design principles of biological networks containing these motifs and can help devise optimal strategies for the integration of these motifs into larger synthetic networks.

Item Type: Journal Article
Publication: Biomolecules
Publisher: MDPI
Additional Information: The copyright for this article belongs to the Authors.
Keywords: article; cell differentiation; gene regulatory network; physiological feedback, Cell Differentiation; Feedback, Physiological; Gene Regulatory Networks
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 27 Jan 2023 09:39
Last Modified: 27 Jan 2023 09:39
URI: https://eprints.iisc.ac.in/id/eprint/79559

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