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PERIOD-TIMELESS interval timer may require an additional feedback loop.

Kuczenski RS, Hong KC, García-Ojalvo J, Lee KH - PLoS Comput. Biol. (2007)

Bottom Line: In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms.This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon.The possible mechanisms underlying the cytoplasmic "interval timer" created by PERIOD-TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure.

View Article: PubMed Central - PubMed

Affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, United States of America.

ABSTRACT
In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms. This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon. The possible mechanisms underlying the cytoplasmic "interval timer" created by PERIOD-TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure. Incorporation of this additional feedback into a full circadian model produced results that are consistent with previous experimental observations of wild-type protein profiles and numerous mutant phenotypes.

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Models of the Isolated per/tim Loop(A) The simple mass action kinetics model.(B) The serial model is based on a series of intermediate (possibly phosphorylated) PER–TIM states.(C) The feedback model proposes a new role for PER providing positive feedback on the dissociation of cytoplasmic PER–TIM complexes.
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pcbi-0030154-g002: Models of the Isolated per/tim Loop(A) The simple mass action kinetics model.(B) The serial model is based on a series of intermediate (possibly phosphorylated) PER–TIM states.(C) The feedback model proposes a new role for PER providing positive feedback on the dissociation of cytoplasmic PER–TIM complexes.

Mentions: To investigate the six-hour delay created by the cytoplasmic interval timer observed in S2 cell culture by Meyer et al. [21], the dynamics of the per/tim loop were isolated and studied independently of the remaining circadian gene network to mimic the environment within Drosophila S2 cells. The interactions constituting the three mathematical models studied are shown in Figure 2. All models of the isolated per/tim loop include PER–TIM dimers in the cytoplasm that dissociate immediately prior to nuclear localization and re-association, but differ in the mechanism controlling the timing of this dissociation.


PERIOD-TIMELESS interval timer may require an additional feedback loop.

Kuczenski RS, Hong KC, García-Ojalvo J, Lee KH - PLoS Comput. Biol. (2007)

Models of the Isolated per/tim Loop(A) The simple mass action kinetics model.(B) The serial model is based on a series of intermediate (possibly phosphorylated) PER–TIM states.(C) The feedback model proposes a new role for PER providing positive feedback on the dissociation of cytoplasmic PER–TIM complexes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1937016&req=5

pcbi-0030154-g002: Models of the Isolated per/tim Loop(A) The simple mass action kinetics model.(B) The serial model is based on a series of intermediate (possibly phosphorylated) PER–TIM states.(C) The feedback model proposes a new role for PER providing positive feedback on the dissociation of cytoplasmic PER–TIM complexes.
Mentions: To investigate the six-hour delay created by the cytoplasmic interval timer observed in S2 cell culture by Meyer et al. [21], the dynamics of the per/tim loop were isolated and studied independently of the remaining circadian gene network to mimic the environment within Drosophila S2 cells. The interactions constituting the three mathematical models studied are shown in Figure 2. All models of the isolated per/tim loop include PER–TIM dimers in the cytoplasm that dissociate immediately prior to nuclear localization and re-association, but differ in the mechanism controlling the timing of this dissociation.

Bottom Line: In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms.This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon.The possible mechanisms underlying the cytoplasmic "interval timer" created by PERIOD-TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure.

View Article: PubMed Central - PubMed

Affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, United States of America.

ABSTRACT
In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms. This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon. The possible mechanisms underlying the cytoplasmic "interval timer" created by PERIOD-TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure. Incorporation of this additional feedback into a full circadian model produced results that are consistent with previous experimental observations of wild-type protein profiles and numerous mutant phenotypes.

Show MeSH
Related in: MedlinePlus