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Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this "presumably transient" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.
This article was published in the following journal.
Name: PLoS computational biology
Feedback loops regulate various biological functions such as oscillations, bistability and robustness. They play a significant role in developmental signalling and failure of feedback can lead to dise...
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Alterations of acid-base equilibrium are very common in critically ill patients and understanding their pathophysiology can be important to improve clinical treatment.
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A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems.
A sub-family of smad proteins that inhibit cell signaling by RECEPTOR-REGULATED SMAD PROTEINS. They form autoinhibitory feedback loops in the TGF-BETA signaling pathway and mediate signaling cross-talk with other signaling pathways
Intracellular signaling adaptor proteins that play a role in the coupling of SYNDECANS to CYTOSKELETAL PROTEINS.
Protein factors that inhibit the dissociation of GDP from GTP-BINDING PROTEINS.
An abundantly-expressed rho GDP-dissociation inhibitor subtype that regulates a broad variety of RHO GTPASES.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...