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BIOMD0000000055 - Locke2005 - Circadian Clock

 

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Reference Publication
Publication ID: 16729048
Locke JC, Southern MM, Kozma-Bognár L, Hibberd V, Brown PE, Turner MS, Millar AJ.
Extension of a genetic network model by iterative experimentation and mathematical analysis.
Mol. Syst. Biol. 2005; 1: 2005.0013
Department of Biological Sciences, University of Warwick, Coventry, UK.  [more]
Model
Original Model: BIOMD0000000055.xml.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL0737170531
Submission Date: 02 May 2006 08:15:42 UTC
Last Modification Date: 24 May 2014 15:38:05 UTC
Creation Date: 02 May 2006 08:15:42 UTC
Encoders:  Harish Dharuri
   Andrew J Millar
set #1
bqbiol:isVersionOf Gene Ontology circadian rhythm
bqbiol:is KEGG Pathway ath04710
bqbiol:hasTaxon Taxonomy Arabidopsis
set #2
bqmodel:isDerivedFrom PubMed 15784272
Notes
Locke2005 - Circadian Clock

SBML model of the interlocked feedback loop network

The model describes the circuit depicted in Fig. 4 and reproduces the simulations in Figure 5A and 5B. It provides initial conditions, parameter values and rules for the production rates of the following species: LHY mRNA (cLm), cytoplasmic LHY (cLc), nuclear LHY (cLn), TOC1 mRNA (cTm), cytoplasmic TOC1 (cTc), nuclear TOC1 (cTn),X mRNA (cXm), cytoplasmic X (cXc), nuclear X (cXn), Y mRNA (cYm), cytoplasmic Y (cYc), nuclear Y (cYn), nuclear P (cPn). This model was successfully tested on MathSBML and SBML ODE Solver.

Fig 5B is not in the right phase. However, the data is correct relative to the light/dark bars at the top of the figure.

This model is described in the article:

Locke JC, Southern MM, Kozma-Bognár L, Hibberd V, Brown PE, Turner MS, Millar AJ
Molecular Systems Biology [2005; 1: 2005.0013]

Abstract:

Circadian clocks involve feedback loops that generate rhythmic expression of key genes. Molecular genetic studies in the higher plant Arabidopsis thaliana have revealed a complex clock network. The first part of the network to be identified, a transcriptional feedback loop comprising TIMING OF CAB EXPRESSION 1 (TOC1), LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), fails to account for significant experimental data. We develop an extended model that is based upon a wider range of data and accurately predicts additional experimental results. The model comprises interlocking feedback loops comparable to those identified experimentally in other circadian systems. We propose that each loop receives input signals from light, and that each loop includes a hypothetical component that had not been explicitly identified. Analysis of the model predicted the properties of these components, including an acute light induction at dawn that is rapidly repressed by LHY and CCA1. We found this unexpected regulation in RNA levels of the evening-expressed gene GIGANTEA (GI), supporting our proposed network and making GI a strong candidate for this component.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 16729048 Submission Date: 02 May 2006 08:15:42 UTC Last Modification Date: 24 May 2014 15:38:05 UTC Creation Date: 02 May 2006 08:15:42 UTC
Mathematical expressions
Reactions
LHY transcription by light activation Light independent LHY transcription LHY mRNA degradation LHY translation
LHY transport out of nucleus Cytoplasmic LHY degradation LHY transport into nucleus Nuclear LHY degradation
TOC1 transcription TOC mRNA degradation TOC1 translation TOC1 transport out of nucleus
Cytoplasmic TOC1 degradation TOC1 movement into nucleus Nuclear TOC1 degradation Protein X transcription
Protein X degradation Protein X translation ProteinX movement out of nucleus Cytoplasmic Protein X degradation
Protein X movement into nucleus Nuclear Protein X degradation Protein Y transcription Protein Y mRNA degradation
Protein Y translation Protein Y out of nucleus Cytoplasmic Protein Y degradation Protein Y into nucleus
Nuclear Protein Y degradation Light dependent production of Protein P Protein P degradation Light activated Protein P degradation
Physical entities
Compartments Species
compartment LHY mRNA LHY protein in cytoplasm LHY protein in nucleus
TOC1 mRNA TOC1 protein in cytoplasm TOC1 protein in nucleus
X mRNA X protein in cytoplasm X protein in nucleus
Y mRNA Y protein in cytoplasm Y protein in nucleus
light sensitive protein P    
Global parameters
q1 n1 a g1
m1 k1 p1 r1
r2 m2 k2 m3
k3 n2 b g2
g3 c m4 k4
p2 r3 r4 m5
m6 k5 m7 m8
k6 n3 d g4
m9 k7 p3 r5
r6 m10 k8 m11
k9 q2 n4 n5
g5 g6 f e
m12 k10 p4 r7
r8 m13 k11 m14
k12 p5 k13 q3
m15 Lmax Lmin CP
dayLength      
Reactions (32)
 
 LHY transcription by light activation  → [LHY mRNA];   {light sensitive protein P}
 
 Light independent LHY transcription  → [LHY mRNA];   {X protein in nucleus}
 
 LHY mRNA degradation [LHY mRNA] → ;  
 
 LHY translation  → [LHY protein in cytoplasm];   {LHY mRNA}
 
 LHY transport out of nucleus [LHY protein in nucleus] → [LHY protein in cytoplasm];  
 
 Cytoplasmic LHY degradation [LHY protein in cytoplasm] → ;  
 
 LHY transport into nucleus [LHY protein in cytoplasm] → [LHY protein in nucleus];  
 
 Nuclear LHY degradation [LHY protein in nucleus] → ;  
 
 TOC1 transcription  → [TOC1 mRNA];   {Y protein in nucleus} , {LHY protein in nucleus}
 
 TOC mRNA degradation [TOC1 mRNA] → ;  
 
 TOC1 translation  → [TOC1 protein in cytoplasm];   {TOC1 mRNA}
 
 TOC1 transport out of nucleus [TOC1 protein in nucleus] → [TOC1 protein in cytoplasm];  
 
 Cytoplasmic TOC1 degradation [TOC1 protein in cytoplasm] → ;  
 
 TOC1 movement into nucleus [TOC1 protein in cytoplasm] → [TOC1 protein in nucleus];  
 
 Nuclear TOC1 degradation [TOC1 protein in nucleus] → ;  
 
 Protein X transcription  → [X mRNA];   {TOC1 protein in nucleus}
 
 Protein X degradation [X mRNA] → ;  
 
 Protein X translation  → [X protein in cytoplasm];   {X mRNA}
 
 ProteinX movement out of nucleus [X protein in nucleus] → [X protein in cytoplasm];  
 
 Cytoplasmic Protein X degradation [X protein in cytoplasm] → ;  
 
 Protein X movement into nucleus [X protein in cytoplasm] → [X protein in nucleus];  
 
 Nuclear Protein X degradation [X protein in nucleus] → ;  
 
 Protein Y transcription  → [Y mRNA];   {light sensitive protein P} , {TOC1 protein in nucleus} , {LHY protein in nucleus}
 
 Protein Y mRNA degradation [Y mRNA] → ;  
 
 Protein Y translation  → [Y protein in cytoplasm];   {Y mRNA}
 
 Protein Y out of nucleus [Y protein in nucleus] → [Y protein in cytoplasm];  
 
 Cytoplasmic Protein Y degradation [Y protein in cytoplasm] → ;  
 
 Protein Y into nucleus [Y protein in cytoplasm] → [Y protein in nucleus];  
 
 Nuclear Protein Y degradation [Y protein in nucleus] → ;  
 
 Light dependent production of Protein P  → [light sensitive protein P];  
 
 Protein P degradation [light sensitive protein P] → ;  
 
 Light activated Protein P degradation [light sensitive protein P] → ;  
 
Functions (1)
 
 LD lambda(tod, length, ceil(sin(pi*tod/length+0.001)/2))
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 LHY mRNA
Compartment: compartment
Initial concentration: 0.539
 
 LHY protein in cytoplasm
Compartment: compartment
Initial concentration: 0.015
 
 LHY protein in nucleus
Compartment: compartment
Initial concentration: 0.0855
 
 TOC1 mRNA
Compartment: compartment
Initial concentration: 0.456
 
 TOC1 protein in cytoplasm
Compartment: compartment
Initial concentration: 8.7
 
 TOC1 protein in nucleus
Compartment: compartment
Initial concentration: 0.4
 
 X mRNA
Compartment: compartment
Initial concentration: 0.08
 
 X protein in cytoplasm
Compartment: compartment
Initial concentration: 1.34
 
 X protein in nucleus
Compartment: compartment
Initial concentration: 0.4
 
 Y mRNA
Compartment: compartment
Initial concentration: 0.037
 
 Y protein in cytoplasm
Compartment: compartment
Initial concentration: 0.0040
 
 Y protein in nucleus
Compartment: compartment
Initial concentration: 0.013
 
 light sensitive protein P
Compartment: compartment
Initial concentration: 0.835
 
Global Parameters (65)
 
 q1
Value: 2.4514
Constant
 
 n1
Value: 5.1694
Constant
 
 a
Value: 3.3064
Constant
 
 g1
Value: 0.876738488
Constant
 
 m1
Value: 1.5283
Constant
 
 k1
Value: 1.817
Constant
 
 p1
Value: 0.8295
Constant
 
 r1
Value: 16.8363
Constant
 
 r2
Value: 0.1687
Constant
 
 m2
Value: 20.44
Constant
 
 k2
Value: 1.5644
Constant
 
 m3
Value: 3.6888
Constant
 
 k3
Value: 1.2765
Constant
 
 n2
Value: 3.0087
Constant
 
 b
Value: 1.0258
Constant
 
 g2
Value: 0.036805783
Constant
 
 g3
Value: 0.26593318
Constant
 
 c
Value: 1.0258
Constant
 
 m4
Value: 3.8231
Constant
 
 k4
Value: 2.5734
Constant
 
 p2
Value: 4.324
Constant
 
 r3
Value: 0.3166
Constant
 
 r4
Value: 2.1509
Constant
 
 m5
Value: 0.0013
Constant
 
 m6
Value: 3.1741
Constant
 
 k5
Value: 2.7454
Constant
 
 m7
Value: 0.0492
Constant
 
 m8
Value: 4.0424
Constant
 
 k6
Value: 0.4033
Constant
 
 n3
Value: 0.2431
Constant
 
 d
Value: 1.4422
Constant
 
 g4
Value: 0.538811228
Constant
 
 m9
Value: 10.1132
Constant
 
 k7
Value: 6.5585
Constant
 
 p3
Value: 2.147
Constant
 
 r5
Value: 1.0352
Constant
 
 r6
Value: 3.3017
Constant
 
 m10
Value: 0.2179
Constant
 
 k8
Value: 0.6632
Constant
 
 m11
Value: 3.3442
Constant
 
 k9
Value: 17.1111
Constant
 
 q2
Value: 2.40178
Constant
 
 n4
Value: 0.0857
Constant
 
 n5
Value: 0.1649
Constant
 
 g5
Value: 1.17803247
Constant
 
 g6
Value: 0.064455137
Constant
 
 f
Value: 1.0237
Constant
 
 e
Value: 3.6064
Constant
 
 m12
Value: 4.297
Constant
 
 k10
Value: 1.7303
Constant
 
 p4
Value: 0.2485
Constant
 
 r7
Value: 2.2123
Constant
 
 r8
Value: 0.2002
Constant
 
 m13
Value: 0.1347
Constant
 
 k11
Value: 1.8258
Constant
 
 m14
Value: 0.6114
Constant
 
 k12
Value: 1.8066
Constant
 
 p5
Value: 0.5
Constant
 
 k13
Value: 1.2
Constant
 
 q3
Value: 1.0
Constant
 
 m15
Value: 1.2
Constant
 
   Lmax
Value: 1.0
Constant
 
   Lmin
Constant
 
   CP
Value: 24.0
Constant
 
   dayLength
Value: 12.0
Constant
 
Light independent LHY transcription (1)
 
   Fch_0
Value: 8.0
Constant
 
Cytoplasmic LHY degradation (1)
 
   Fch_0
Value: 8.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000055

Curator's comment: (updated: 18 Jan 2010 15:08:46 GMT)

The model reproduces figure 5A and 5B of the reference publication. The model was integrated and simulated using Copasi v4.5 (Build 30)

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