PERIOD-TIMELESS interval timer may require an additional feedback loop.
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.
School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, United States of America.
Robert S
RS
Kuczenski
Kevin C
KC
Hong
Jordi
J
García-Ojalvo
Kelvin H
KH
Lee
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003198:Computer Simulation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005246:Feedback / Q000502:physiology*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D009991:Oscillometry / Q000379:methods; D056950:Period Circadian Proteins; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
D029721:Drosophila Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C096445:tim protein, Drosophila