Short description
Related Publication
  • A reduced model clarifies the role of feedback loops and time delays in the Drosophila circadian oscillator.
  • Smolen P, Baxter DA, Byrne JH
  • Biophysical journal , 11/ 2002 , Volume 83 , pages: 2349-2359
  • Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas-Houston Medical School, Houston, TX 77225, USA.
  • Although several detailed models of molecular processes essential for circadian oscillations have been developed, their complexity makes intuitive understanding of the oscillation mechanism difficult. The goal of the present study was to reduce a previously developed, detailed model to a minimal representation of the transcriptional regulation essential for circadian rhythmicity in Drosophila. The reduced model contains only two differential equations, each with time delays. A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor. A positive feedback loop is also included, in which dCLOCK indirectly enhances its own formation. The model simulated circadian oscillations, light entrainment, and a phase-response curve with qualitative similarities to experiment. Time delays were found to be essential for simulation of circadian oscillations with this model. To examine the robustness of the simplified model to fluctuations in molecule numbers, a stochastic variant was constructed. Robust circadian oscillations and entrainment to light pulses were simulated with fewer than 80 molecules of each gene product present on average. Circadian oscillations persisted when the positive feedback loop was removed. Moreover, elimination of positive feedback did not decrease the robustness of oscillations to stochastic fluctuations or to variations in parameter values. Such reduced models can aid understanding of the oscillation mechanisms in Drosophila and in other organisms in which feedback regulation of transcription may play an important role.
Nicolas Le Novère

Metadata information

BioModels Database MODEL6618294363
BioModels Database BIOMD0000000025
KEGG Pathway dme04710
PubMed 12414672
PubMed 11517254
Curation status
  • Model originally submitted by : Nicolas Le Novère
  • Submitted: Sep 13, 2005 2:31:54 PM
  • Last Modified: Feb 25, 2015 12:51:28 PM
  • Version: 2 public model Download this version
    • Submitted on: Feb 25, 2015 12:51:28 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of Smolen2002_CircClock
  • Version: 1 public model Download this version
    • Submitted on: Sep 13, 2005 2:31:54 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of Smolen2002_CircClock
Curator's comment:
(added: 22 Sep 2010, 11:17:42, updated: 22 Sep 2010, 11:17:42)
Reproduction of figure 1 of the original publication using octave. To simulate this model, the sbml file first was translated to matlab using the SBW online translator ( A function to intra- and extrapolate the delayed variables was added and the time course simulated using ode23. The changes to the code and detailed instruction on how to perform the simulations are available on demand, and, hopefully soon, from our FAQ. As the initial conditions are not known, the time course is different from the published results for the first 15 hours and the oscillations are shifted.