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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.

Show MeSH
The Effect of Gene Dosage on the Period of Oscillation in Constant DarknessA continuation analysis of per dosage-dependent behavior of period under constant darkness (black line) shows an inverse relation between the maximum transcription activation of per and the period length, which is consistent with the experimental results (represented by black squares and error bars) [29,30]. A continuation analysis of tim dosage-dependent behavior of period under constant darkness (gray line) shows a similar trend to per dosage, which is inconsistent with experimental observations (represented by gray circles and error bars) [17,31].
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pcbi-0030154-g007: The Effect of Gene Dosage on the Period of Oscillation in Constant DarknessA continuation analysis of per dosage-dependent behavior of period under constant darkness (black line) shows an inverse relation between the maximum transcription activation of per and the period length, which is consistent with the experimental results (represented by black squares and error bars) [29,30]. A continuation analysis of tim dosage-dependent behavior of period under constant darkness (gray line) shows a similar trend to per dosage, which is inconsistent with experimental observations (represented by gray circles and error bars) [17,31].

Mentions: Our results show a per dosage dependence of the period length that is consistent with experimental observations [29,30]. A continuation analysis of the maximum transcriptional activation of per in the model demonstrates an inverse relation between per dosage and the period of circadian oscillation (black lines and points in Figure 7). In contrast, a continuation analysis of the maximum transcriptional activation of tim (gray lines and points in Figure 7) revealed a profile which is similar to per dosage and thus not very consistent with experimental observations [17,31].


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

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

The Effect of Gene Dosage on the Period of Oscillation in Constant DarknessA continuation analysis of per dosage-dependent behavior of period under constant darkness (black line) shows an inverse relation between the maximum transcription activation of per and the period length, which is consistent with the experimental results (represented by black squares and error bars) [29,30]. A continuation analysis of tim dosage-dependent behavior of period under constant darkness (gray line) shows a similar trend to per dosage, which is inconsistent with experimental observations (represented by gray circles and error bars) [17,31].
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0030154-g007: The Effect of Gene Dosage on the Period of Oscillation in Constant DarknessA continuation analysis of per dosage-dependent behavior of period under constant darkness (black line) shows an inverse relation between the maximum transcription activation of per and the period length, which is consistent with the experimental results (represented by black squares and error bars) [29,30]. A continuation analysis of tim dosage-dependent behavior of period under constant darkness (gray line) shows a similar trend to per dosage, which is inconsistent with experimental observations (represented by gray circles and error bars) [17,31].
Mentions: Our results show a per dosage dependence of the period length that is consistent with experimental observations [29,30]. A continuation analysis of the maximum transcriptional activation of per in the model demonstrates an inverse relation between per dosage and the period of circadian oscillation (black lines and points in Figure 7). In contrast, a continuation analysis of the maximum transcriptional activation of tim (gray lines and points in Figure 7) revealed a profile which is similar to per dosage and thus not very consistent with experimental observations [17,31].

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