Leloup1999_CircadianRhythms_Drosophila

  public model
Model Identifier
BIOMD0000000298
Short description

This a model from the article:
Limit cycle models for circadian rhythms based on transcriptional regulation in Drosophila and Neurospora.
Leloup JC, Gonze D, Goldbeter A. J Biol Rhythms.1999 Dec;14(6):433-48. 10643740,
Abstract:
We examine theoretical models for circadian oscillations based on transcriptional regulation in Drosophila and Neurospora. For Drosophila, the molecular model is based on the negative feedback exerted on the expression of the per and tim genes by the complex formed between the PER and TIM proteins. For Neurospora, similarly, the model relies on the feedback exerted on the expression of the frq gene by its protein product FRQ. In both models, sustained rhythmic variations in protein and mRNA levels occur in continuous darkness, in the form of limit cycle oscillations. The effect of light on circadian rhythms is taken into account in the models by considering that it triggers degradation of the TIM protein in Drosophila, and frq transcription in Neurospora. When incorporating the control exerted by light at the molecular level, we show that the models can account for the entrainment of circadian rhythms by light-dark cycles and for the damping of the oscillations in constant light, though such damping occurs more readily in the Drosophila model. The models account for the phase shifts induced by light pulses and allow the construction of phase response curves. These compare well with experimental results obtained in Drosophila. The model for Drosophila shows that when applied at the appropriate phase, light pulses of appropriate duration and magnitude can permanently or transiently suppress circadian rhythmicity. We investigate the effects of the magnitude of light-induced changes on oscillatory behavior. Finally, we discuss the common and distinctive features of circadian oscillations in the two organisms.

This particular version of the model has been translated from equations 1a-1j (Drosophila).

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Leloup JC, Gonze D, Goldbeter A. (1999) - version02
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@aukland.ac.nz
The University of Auckland
The Bioengineering Institute

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V3)
Related Publication
  • Limit cycle models for circadian rhythms based on transcriptional regulation in Drosophila and Neurospora.
  • Leloup JC, Gonze D, Goldbeter A
  • Journal of biological rhythms , 12/ 1999 , Volume 14 , pages: 433-448 , PubMed ID: 10643740
  • Faculté des Sciences, Université Libre de Bruxelles, Brussels, Belgium.
  • We examine theoretical models for circadian oscillations based on transcriptional regulation in Drosophila and Neurospora. For Drosophila, the molecular model is based on the negative feedback exerted on the expression of the per and tim genes by the complex formed between the PER and TIM proteins. For Neurospora, similarly, the model relies on the feedback exerted on the expression of the frq gene by its protein product FRQ. In both models, sustained rhythmic variations in protein and mRNA levels occur in continuous darkness, in the form of limit cycle oscillations. The effect of light on circadian rhythms is taken into account in the models by considering that it triggers degradation of the TIM protein in Drosophila, and frq transcription in Neurospora. When incorporating the control exerted by light at the molecular level, we show that the models can account for the entrainment of circadian rhythms by light-dark cycles and for the damping of the oscillations in constant light, though such damping occurs more readily in the Drosophila model. The models account for the phase shifts induced by light pulses and allow the construction of phase response curves. These compare well with experimental results obtained in Drosophila. The model for Drosophila shows that when applied at the appropriate phase, light pulses of appropriate duration and magnitude can permanently or transiently suppress circadian rhythmicity. We investigate the effects of the magnitude of light-induced changes on oscillatory behavior. Finally, we discuss the common and distinctive features of circadian oscillations in the two organisms.
Contributors
Vijayalakshmi Chelliah

Metadata information

is
BioModels Database MODEL0478965170
BioModels Database BIOMD0000000298
isDerivedFrom
BioModels Database BIOMD0000000171
isDescribedBy
PubMed 10643740
hasTaxon
isVersionOf
isPartOf
KEGG Pathway dme04710

Curation status
Curated

Original model(s)
http://www.cellml.org/models/leloup_gonze_goldbeter_1999_version02

Tags
Name Description Size Actions

Model files

BIOMD0000000298_url.xml SBML L2V3 representation of Leloup1999_CircadianRhythms_Drosophila 31.20 KB Preview | Download

Additional files

BIOMD0000000298-biopax3.owl Auto-generated BioPAX (Level 3) 8.04 KB Preview | Download
BIOMD0000000298.xpp Auto-generated XPP file 4.54 KB Preview | Download
BIOMD0000000298-biopax2.owl Auto-generated BioPAX (Level 2) 7.03 KB Preview | Download
BIOMD0000000298.m Auto-generated Octave file 7.73 KB Preview | Download
BIOMD0000000298.pdf Auto-generated PDF file 157.68 KB Preview | Download
BIOMD0000000298.svg Auto-generated Reaction graph (SVG) 851.00 Bytes Preview | Download
BIOMD0000000298.sci Auto-generated Scilab file 4.13 KB Preview | Download
BIOMD0000000298.vcml Auto-generated VCML file 900.00 Bytes Preview | Download
BIOMD0000000298.png Auto-generated Reaction graph (PNG) 5.04 KB Preview | Download
BIOMD0000000298_urn.xml Auto-generated SBML file with URNs 30.75 KB Preview | Download

  • Model originally submitted by : Vijayalakshmi Chelliah
  • Submitted: 28-Apr-2009 16:31:24
  • Last Modified: 25-Feb-2015 13:41:24
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 25-Feb-2015 13:41:24
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Current version of Leloup1999_CircadianRhythms_Drosophila
  • Version: 1 public model Download this version
    • Submitted on: 28-Apr-2009 16:31:24
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Original import of Leloup1999_CircadianRhythms

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
MT = vsT*KIT^n/(KIT^n+CN^n)-(vmT*MT/(KmT+MT)+kd*MT) vsT*KIT^n/(KIT^n+CN^n)-(vmT*MT/(KmT+MT)+kd*MT) kd = 0.01; n = 4.0; vsT = 1.0; KIT = 1.0; KmT = 0.2; vmT = 0.7
P0 = (ksP*MP+V2P*P1/(K2P+P1))-(V1P*P0/(K1P+P0)+kd*P0) (ksP*MP+V2P*P1/(K2P+P1))-(V1P*P0/(K1P+P0)+kd*P0) kd = 0.01; V1P = 8.0; V2P = 1.0; K2P = 2.0; K1P = 2.0; ksP = 0.9
P1 = (V1P*P0/(K1P+P0)+V4P*P2/(K4P+P2))-(V2P*P1/(K2P+P1)+V3P*P1/(K3P+P1)+kd*P1) (V1P*P0/(K1P+P0)+V4P*P2/(K4P+P2))-(V2P*P1/(K2P+P1)+V3P*P1/(K3P+P1)+kd*P1) V4P = 1.0; kd = 0.01; V1P = 8.0; V2P = 1.0; K1P = 2.0; K2P = 2.0; K3P = 2.0; K4P = 2.0; V3P = 8.0
MP = vsP*KIP^n/(KIP^n+CN^n)-(vmP*MP/(KmP+MP)+kd*MP) vsP*KIP^n/(KIP^n+CN^n)-(vmP*MP/(KmP+MP)+kd*MP) kd = 0.01; n = 4.0; KIP = 1.0; vmP = 1.0; KmP = 0.2; vsP = 1.1
CN = k1*C-(k2*CN+kdN*CN) k1*C-(k2*CN+kdN*CN) k2 = 0.2; k1 = 0.8; kdN = 0.01
C = (k3*P2*T2+k2*CN)-(k4*C+k1*C+kdC*C) (k3*P2*T2+k2*CN)-(k4*C+k1*C+kdC*C) k2 = 0.2; k1 = 0.8; k4 = 0.6; k3 = 1.2; kdC = 0.01
T2 = (V3T*T1/(K3T+T1)+k4*C)-(V4T*T2/(K4T+T2)+k3*P2*T2+vdT*T2/(KdT+T2)+kd*T2) (V3T*T1/(K3T+T1)+k4*C)-(V4T*T2/(K4T+T2)+k3*P2*T2+vdT*T2/(KdT+T2)+kd*T2) kd = 0.01; V3T = 8.0; K3T = 2.0; K4T = 2.0; k4 = 0.6; vdT = 3.0; k3 = 1.2; V4T = 1.0; KdT = 0.2
T1 = (V1T*T0/(K1T+T0)+V4T*T2/(K4T+T2))-(V2T*T1/(K2T+T1)+V3T*T1/(K3T+T1)+kd*T1) (V1T*T0/(K1T+T0)+V4T*T2/(K4T+T2))-(V2T*T1/(K2T+T1)+V3T*T1/(K3T+T1)+kd*T1) V2T = 1.0; kd = 0.01; V3T = 8.0; K3T = 2.0; K2T = 2.0; K4T = 2.0; V1T = 8.0; K1T = 2.0; V4T = 1.0
T0 = (ksT*MT+V2T*T1/(K2T+T1))-(V1T*T0/(K1T+T0)+kd*T0) (ksT*MT+V2T*T1/(K2T+T1))-(V1T*T0/(K1T+T0)+kd*T0) V2T = 1.0; kd = 0.01; ksT = 0.9; K2T = 2.0; V1T = 8.0; K1T = 2.0
P2 = (V3P*P1/(K3P+P1)+k4*C)-(V4P*P2/(K4P+P2)+k3*P2*T2+vdP*P2/(KdP+P2)+kd*P2) (V3P*P1/(K3P+P1)+k4*C)-(V4P*P2/(K4P+P2)+k3*P2*T2+vdP*P2/(KdP+P2)+kd*P2) V4P = 1.0; kd = 0.01; KdP = 0.2; K3P = 2.0; k4 = 0.6; K4P = 2.0; V3P = 8.0; k3 = 1.2; vdP = 2.2
Curator's comment:
(added: 14 Jan 2011, 14:20:07, updated: 14 Jan 2011, 14:20:07)
The model reproduces figure 2a of the reference publication. The model was integrated and simulated using Copasi v4.6 (Build 32).