 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, September 1, 2001, 21(17):6644-6656
Modeling Circadian Oscillations with Interlocking Positive and Negative Feedback Loops
Paul Smolen, Douglas A. Baxter, and John H. Byrne Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas-Houston Medical School, Houston, Texas
Both positive and negative feedback loops of transcriptional regulation have been proposed to be important for the generation of circadian rhythms. To test the sufficiency of the proposed mechanisms, two differential equation-based models were constructed to describe the Neurospora crassa and Drosophila melanogaster circadian oscillators. In the model of the Neurospora oscillator, FRQ suppresses frq transcription by binding to a complex of the transcriptional activators WC-1 and WC-2, thus yielding negative feedback. FRQ also activates synthesis of WC-1, which in turn activates frq transcription, yielding positive feedback. In the model of the Drosophila oscillator, PER and TIM are represented by a "lumped" variable, "PER." PER suppresses its own transcription by binding to the transcriptional regulator dCLOCK, thus yielding negative feedback. PER also binds to dCLOCK to de-repress dclock, and dCLOCK in turn activates per transcription, yielding positive feedback. Both models displayed circadian oscillations that were robust to parameter variations and to noise and that entrained to simulated light/dark cycles. Circadian oscillations were only obtained if time delays were included to represent processes not modeled in detail (e.g., transcription and translation). In both models, oscillations were preserved when positive feedback was removed.
Key words: circadian; Drosophila; Neurospora; PER; CLOCK; FRQ; positive feedback; simulation
Copyright © 2001 Society for Neuroscience 0270-6474/01/21176644-13$05.00/0
This article has been cited by other articles:
C. Gerard, D. Gonze, and A. Goldbeter
Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations
Phil Trans R Soc A, December 13, 2009; 367(1908): 4665 - 4683.
[Abstract] [Full Text] [PDF]
H. P. Mirsky, A. C. Liu, D. K. Welsh, S. A. Kay, and F. J. Doyle III
A model of the cell-autonomous mammalian circadian clock
PNAS, July 7, 2009; 106(27): 11107 - 11112.
[Abstract] [Full Text] [PDF]
Junwei Wang, Jiajun Zhang, Zhanjiang Yuan, Aimin Chen, and Tianshou Zhou
Neurotransmitter-Mediated Collective Rhythms in Grouped Drosophila Circadian Clocks
J Biol Rhythms, December 1, 2008; 23(6): 472 - 482.
[Abstract] [PDF]
N. A. Dunn, J. S. Conery, and S. R. Lockery
Circuit Motifs for Spatial Orientation Behaviors Identified by Neural Network Optimization
J Neurophysiol, August 1, 2007; 98(2): 888 - 897.
[Abstract] [Full Text] [PDF]
Y. Yu, W. Dong, C. Altimus, X. Tang, J. Griffith, M. Morello, L. Dudek, J. Arnold, and H.-B. Schuttler
A genetic network for the clock of Neurospora crassa
PNAS, February 20, 2007; 104(8): 2809 - 2814.
[Abstract] [Full Text] [PDF]
N. Bagheri, J. Stelling, and F. J. Doyle III
Quantitative performance metrics for robustness in circadian rhythms
Bioinformatics, February 1, 2007; 23(3): 358 - 364.
[Abstract] [Full Text] [PDF]
F. J Doyle III and J. Stelling
Systems interface biology
J R Soc Interface, October 22, 2006; 3(10): 603 - 616.
[Abstract] [Full Text] [PDF]
P. Indic, K. Gurdziel, R. E. Kronauer, and E. B. Klerman
Development of a Two-Dimension Manifold to Represent High Dimension Mathematical Models of the Intracellular Mammalian Circadian Clock
J Biol Rhythms, June 1, 2006; 21(3): 222 - 232.
[Abstract] [PDF]
Y. Zhurov and V. Brezina
Temperature Compensation of Neuromuscular Modulation in Aplysia
J Neurophysiol, November 1, 2005; 94(5): 3259 - 3277.
[Abstract] [Full Text] [PDF]
A. Wagner
Circuit topology and the evolution of robustness in two-gene circadian oscillators
PNAS, August 16, 2005; 102(33): 11775 - 11780.
[Abstract] [Full Text] [PDF]
J. C. Dunlap and J. J. Loros
The Neurospora Circadian System
J Biol Rhythms, October 1, 2004; 19(5): 414 - 424.
[Abstract] [PDF]
J. Stelling, E. D. Gilles, and F. J. Doyle III
From the Cover: Robustness properties of circadian clock architectures
PNAS, September 7, 2004; 101(36): 13210 - 13215.
[Abstract] [Full Text] [PDF]
D. B. Forger and C. S. Peskin
A detailed predictive model of the mammalian circadian clock
PNAS, December 9, 2003; 100(25): 14806 - 14811.
[Abstract] [Full Text] [PDF]
P. Smolen and J. H. Byrne
Support of Progress in Clinical Neurology by Models of Genetic Regulation
Arch Neurol, August 1, 2003; 60(8): 1053 - 1057.
[Abstract] [Full Text] [PDF]
J.-C. Leloup and A. Goldbeter
Toward a detailed computational model for the mammalian circadian clock
PNAS, June 10, 2003; 100(12): 7051 - 7056.
[Abstract] [Full Text] [PDF]
Y. Lin, M. Han, B. Shimada, L. Wang, T. M. Gibler, A. Amarakone, T. A. Awad, G. D. Stormo, R. N. Van Gelder, and P. H. Taghert
Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophilamelanogaster
PNAS, July 9, 2002; 99(14): 9562 - 9567.
[Abstract] [Full Text] [PDF]
J. M. G. Vilar, H. Y. Kueh, N. Barkai, and S. Leibler
Mechanisms of noise-resistance in genetic oscillators
PNAS, April 30, 2002; 99(9): 5988 - 5992.
[Abstract] [Full Text] [PDF]
R. N. Van Gelder
Tales from the Crypt(ochromes)
J Biol Rhythms, April 1, 2002; 17(2): 110 - 120.
[Abstract] [PDF]
D. Gonze, J. Halloy, and A. Goldbeter
Robustness of circadian rhythms with respect to molecular noise
PNAS, January 22, 2002; 99(2): 673 - 678.
[Abstract] [Full Text] [PDF]
J. M. G. Vilar, H. Y. Kueh, N. Barkai, and S. Leibler
Mechanisms of noise-resistance in genetic oscillators
PNAS, April 30, 2002; 99(9): 5988 - 5992.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|