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xie1

xie1

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Reactions

re1

CC PT association

CC + PT > CCPT

re10

clkm translation

∅ > CLK

re15

Degradation of per mRNA

perm > ∅

re17

perm translation

∅ > PER

re2

Degradation of CLK CYK dimer

CC > ∅

re20

per transcription

∅ > perm

re28

vri transcription

∅ > vrim

re3

Degradation of CC PT dimer

CCPT > ∅

re30

Degradation of vri mRNA

vrim > ∅

re31

vrim translation

∅ > VRI

re32

VRI protein degradation

VRI > ∅

re35

pdp transcription

∅ > pdpm

re37

Degradation of pdp mRNA

pdpm > ∅

re38

pdpm translation

∅ > PDP

re39

PDP protein degradation

PDP > ∅

re4

Degradation of PER TIM dimer

PT > ∅

re42

clk transcription

∅ > clkm

re43

CLK CYC association

CLK + CYC > CC

re44

CLK protein degradation

CLK > ∅

re45

CLK CYC dissociation

CC > CLK + CYC

re46

PER TIM association

PER + TIM > PT

re47

PER TIM dissociation

PT > PER + TIM

re48

PER protein degradation

PER > ∅

re51

tim transcription

∅ > timm

re53

Degradation of tim mRNA

timm > ∅

re54

timm translation

∅ > TIM

re55

TIM protein degradation

TIM > ∅

re56

CC PT dimer dissociation

CCPT > CC + PT

re57

CC binding probability in per promoter

∅ > prcper

re58

CC Unbinding probability in per promoter

prcper > ∅

re59

CC Unbinding probability in vri promoter

prcv > ∅

re60

CC binding probability in vri promoter

∅ > prcv

re61

CC Unbinding probability in pdp1 promoter

prcpdp > ∅

re62

CC binding probability in pdp1 promoter

∅ > prcpdp

re63

VRI binding clk promoter

∅ > prvc

re64

VRI unbinding clk promoter

prvc > ∅

re65

PDP binding clk promoter

∅ > prpc

re66

PDP unbinding clk promoter

prpc > ∅

re68

CC binding probability in tim promoter

∅ > prct

re69

CC Unbinding probability in tim promoter

prct > ∅

re9

Degradation of clk mRNA

clkm > ∅

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Modelling of circadian rhythms in Drosophila incorporating the interlocked PER/TIM and VRI/PDP1 feedback loops.

  • Z Xie
  • D Kulasiri
J. Theor. Biol. 2007; 245 (2): 290
Abstract
Circadian rhythms of gene activity, metabolism, physiology and behaviour are observed in all the eukaryotes and some prokaryotes. In this study, we present a model to represent the transcriptional regulatory network essential for the circadian rhythmicity in Drosophila. The model incorporates the transcriptional feedback loops revealed so far in the network of the circadian clock (PER/TIM and VRI/PDP1 loops). Conventional Hill functions are not assumed to describe the regulation of genes, instead of the explicit reactions of binding and unbinding processes of transcription factors to promoters are modelled. The model simulates sustained circadian oscillations in mRNA and protein concentrations in constant darkness in agreement with experimental observations. It also simulates entrainment by light-dark cycles, disappearance of the rhythmicity in constant light and the shape of phase response curves resembling that of the experimental results. The model is robust over a wide range of parameter variations. In addition, the simulated E-box mutation, per(S) and per(L) mutants are similar to that observed in the experiments. The deficiency between the simulated mRNA levels and experimental observations in per(01), tim(01) and clk(Jrk) mutants suggests some difference on the part of the model from reality.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000160) Biomodels notes: Plot corresponds to Fig 3 of the paper. Results obtained from MathSBML. JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.