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• W2022756896 abstract "Previous studies showed that a single negative feedback structure should be sufficient for robust circadian oscillations. It is thus pertinent to ask why current cellular clock models almost universally have interlocked negative feedback loop (NFL) and positive feedback loop (PFL). Here, we propose a molecular model that reflects the essential features of the Drosophila circadian clock to clarify the different roles of negative and positive feedback loops. In agreement with experimental observations, the model can simulate circadian oscillations in constant darkness, entrainment by light–dark cycles, as well as phenotypes of per01 and clkJrk mutants. Moreover, sustained oscillations persist when the PFL is removed, implying the crucial role of NFL for rhythm generation. Through parameter sensitivity analysis, it is revealed that incorporation of PFL increases the robustness of the system to regulatory processes in PFL itself. Such reduced models can aid understanding of the design principles of circadian clocks in Drosophila and other organisms with complex transcriptional feedback structures." @default.
• W2022756896 created "2016-06-24" @default.
• W2022756896 creator A5039634984 @default.
• W2022756896 creator A5050747336 @default.
• W2022756896 date "2010-06-01" @default.
• W2022756896 modified "2023-10-18" @default.
• W2022756896 title "A computational model clarifies the roles of positive and negative feedback loops in the Drosophila circadian clock" @default.
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• W2022756896 doi "https://doi.org/10.1016/j.physleta.2010.04.059" @default.
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