Pokhilko2012_CircClock_RepressilatorFeedbackloop

  public model
Model Identifier
BIOMD0000000412
Short description

This model is from the article:
The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops
Pokhilko A, Fernández AP, Edwards KD, Southern MM, Halliday KJ, Millar AJ. Mol Syst Biol.2012 Mar 6;8:574. 22395476,
Abstract:
Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene PSEUDO-RESPONSE REGULATOR 9 was repressed by an evening gene, previously identified with TIMING OF CAB EXPRESSION1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes LATE ELONGATED HYPOCOTYL and CIRCADIAN CLOCK ASSOCIATED1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure.

Format
SBML (L2V4)
Related Publication
  • The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.
  • Pokhilko A, Fern├índez AP, Edwards KD, Southern MM, Halliday KJ, Millar AJ
  • Molecular Systems Biology , 3/ 2012 , Volume 8 , pages: 574 , PubMed ID: 22395476
  • School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
  • Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene Pseudo-Response Regulator 9 was repressed by an evening gene, previously identified with Timing Of CAB Expression1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes Late Elongated Hypocotyl and Circadian Clock Associated1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure.
Contributors
Alexandra Pokhilko

Metadata information

is
BioModels Database MODEL1109200000
BioModels Database BIOMD0000000412
isDerivedFrom
BioModels Database BIOMD0000000273
isDescribedBy
PubMed 22395476
hasTaxon
isVersionOf

Curation status
Curated

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Model files

BIOMD0000000412_url.xml SBML L2V4 representation of Pokhilko2012_CircClock_RepressilatorFeedbackloop 527.51 KB Preview | Download

Additional files

BIOMD0000000412.pdf Auto-generated PDF file 2.80 KB Preview | Download
BIOMD0000000412.vcml Auto-generated VCML file 953.00 bytes Preview | Download
BIOMD0000000412-biopax3.owl Auto-generated BioPAX (Level 3) 129.04 KB Preview | Download
BIOMD0000000412.svg Auto-generated Reaction graph (SVG) 155.48 KB Preview | Download
BIOMD0000000412.png Auto-generated Reaction graph (PNG) 724.55 KB Preview | Download
BIOMD0000000412-biopax2.owl Auto-generated BioPAX (Level 2) 77.60 KB Preview | Download
BIOMD0000000412_urn.xml Auto-generated SBML file with URNs 525.23 KB Preview | Download
BIOMD0000000412.xpp Auto-generated XPP file 32.53 KB Preview | Download
BIOMD0000000412.m Auto-generated Octave file 38.89 KB Preview | Download
BIOMD0000000412.sci Auto-generated Scilab file 154.00 bytes Preview | Download

  • Model originally submitted by : Alexandra Pokhilko
  • Submitted: Sep 20, 2011 2:12:46 PM
  • Last Modified: Jul 21, 2015 6:52:52 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Jul 21, 2015 6:52:52 PM
    • Submitted by: Alexandra Pokhilko
    • With comment: Current version of Pokhilko2012_CircClock_RepressilatorFeedbackloop
  • Version: 1 public model Download this version
    • Submitted on: Sep 20, 2011 2:12:46 PM
    • Submitted by: Alexandra Pokhilko
    • With comment: Original import of Alex
Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
def*(m3*cL+p3*cL^c/(cL^c+g3^c))/def

def*(m3*cL+p3*cL^c/(cL^c+g3^c))/def
m3 = 0.2; p3 = 0.1; c = 2.0; g3 = 0.6
def*(m39*cLUX+p26*cLUX*p25*cE4*cE3n/(p26*cLUX+p21+m37*cCOP1d+m36*cCOP1n))/def

def*(m39*cLUX+p26*cLUX*p25*cE4*cE3n/(p26*cLUX+p21+m37*cCOP1d+m36*cCOP1n))/def
p25 = 8.0; m37 = 0.8; m36 = 0.1; p26 = 0.3; m39 = 0.3; p21 = 1.0
def*m34*cLUX_m/def

def*m34*cLUX_m/def
m34 = 0.6
def*p3*cL^c/(cL^c+g3^c)/def

def*p3*cL^c/(cL^c+g3^c)/def
p3 = 0.1; c = 2.0; g3 = 0.6
def*m4*cLm/def

def*m4*cLm/def
m4 = 0.2
def*(m17+m24*(1-(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))))*cNI

def*(m17+m24*(1-(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))))*cNI
twilightPeriod = 0.05 3600*s; cyclePeriod = 24.0 3600*s; photoPeriod = 12.0 3600*s; lightOffset = 0.0 3600*s; m24 = 0.1; phase = 0.0 3600*s; m17 = 0.5; lightAmplitude = 1.0 3600*s
def*m16*cNI_m/def

def*m16*cNI_m/def
m16 = 0.5
def*m11*cP*(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))

def*m11*cP*(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))
twilightPeriod = 0.05 3600*s; cyclePeriod = 24.0 3600*s; photoPeriod = 12.0 3600*s; lightOffset = 0.0 3600*s; m11 = 1.0; phase = 0.0 3600*s; lightAmplitude = 1.0 3600*s
def*(n8*(cLm+cL)^e/((cLm+cL)^e+g10^e)+n9*cP9^f/(cP9^f+g11^f))/def

def*(n8*(cLm+cL)^e/((cLm+cL)^e+g10^e)+n9*cP9^f/(cP9^f+g11^f))/def
g11 = 0.7; n9 = 0.2; f = 2.0; g10 = 0.5; n8 = 0.5; e = 2.0
def*m14*cP7_m/def

def*m14*cP7_m/def
m14 = 0.4
def*((((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))*q3*cP+(n4+n7*cL^e/(cL^e+g9^e))*g8/(cEC+g8))

def*((((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))*q3*cP+(n4+n7*cL^e/(cL^e+g9^e))*g8/(cEC+g8))
twilightPeriod = 0.05 3600*s; g9 = 0.3; n7 = 0.2; e = 2.0; cyclePeriod = 24.0 3600*s; q3 = 2.8; g8 = 0.01; photoPeriod = 12.0 3600*s; lightOffset = 0.0 3600*s; phase = 0.0 3600*s; lightAmplitude = 1.0 3600*s; n4 = 0.07
def*((m6+m7*(1-(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))))*cT*(p5*cZTL+cZG)+m8*cT)

def*((m6+m7*(1-(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))))*cT*(p5*cZTL+cZG)+m8*cT)
twilightPeriod = 0.05 3600*s; p5 = 4.0; cyclePeriod = 24.0 3600*s; m8 = 0.4; photoPeriod = 12.0 3600*s; lightOffset = 0.0 3600*s; m6 = 0.3; m7 = 0.7; phase = 0.0 3600*s; lightAmplitude = 1.0 3600*s
def*(p12*(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))*cZTL*cG-p13*(1-(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod))))*cZG)

def*(p12*(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))*cZTL*cG-p13*(1-(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod))))*cZG)
p12 = 3.4; lightOffset = 0.0 3600*s; phase = 0.0 3600*s; twilightPeriod = 0.05 3600*s; cyclePeriod = 24.0 3600*s; photoPeriod = 12.0 3600*s; p13 = 0.1; lightAmplitude = 1.0 3600*s
def*((((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))*q1*cP+n1*g1^a/((cP9+cP7+cNI+cT)^a+g1^a))

def*((((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))*q1*cP+n1*g1^a/((cP9+cP7+cNI+cT)^a+g1^a))
twilightPeriod = 0.05 3600*s; a = 2.0; cyclePeriod = 24.0 3600*s; n1 = 2.6; photoPeriod = 12.0 3600*s; lightOffset = 0.0 3600*s; g1 = 0.1; q1 = 1.2; phase = 0.0 3600*s; lightAmplitude = 1.0 3600*s
def*cL_m*(p1*(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))+p2)

def*cL_m*(p1*(((lightOffset+0.5*lightAmplitude*(1+tanh(cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))/twilightPeriod)))-0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-photoPeriod)/twilightPeriod)))+0.5*lightAmplitude*(1+tanh((cyclePeriod*((time+phase)/cyclePeriod-floor(floor(time+phase)/cyclePeriod))-cyclePeriod)/twilightPeriod)))+p2)
twilightPeriod = 0.05 3600*s; p2 = 0.27; cyclePeriod = 24.0 3600*s; p1 = 0.13; photoPeriod = 12.0 3600*s; lightOffset = 0.0 3600*s; phase = 0.0 3600*s; lightAmplitude = 1.0 3600*s
Curator's comment:
(added: 04 Apr 2012, 13:29:08, updated: 04 Apr 2012, 13:29:08)
The plots corresponding to WT (Wild Type) in figure 2C of the reference publication has been reproduced here. The data were obtained by simulating the model using Copasi v4.8 (Build 35) and plotted using Gnuplot.