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leloup6

leloup6

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CN_decay

nuclear PER_TIM compl. decay

CN > ∅

C_decay

cytopl. PER_TIM compl. decay

C > ∅

C_form

Per_TIM complex formation

P2 + T2 > C

C_transp

PER_TIM complex shuttling

C = CN

M_P_decay

per mRNA decay

M_P > ∅

M_T_decay

tim mRNA decay

M_T > ∅

P1_decay

PER-p decay

P1 > ∅

P1_depho

PER-p dephosphorylation

P1 > P0

P1_pho

PER-p phosphorylation

P1 > P2

P2_decay

PER-pp decay

P2 > ∅

P2_depho

PER-pp dephosphorylation

P2 > P1

P2_light_deact

PER-pp light deactivation

P2 > ∅

PER_transl

PER tranlation

∅ > P0

PO_decay

PER decay

P0 > ∅

P_pho

PER phosphorylation

P0 > P1

T0_decay

TIM decay

T0 > ∅

T1_decay

TIM-p decay

T1 > ∅

T1_depho

TIM-p dephosphorylation

T1 > T0

T1_pho

TIM-p phosphorylation

T1 > T2

T2_decay

TIM-pp decay

T2 > ∅

T2_depho

TIM-pp dephosphorylation

T2 > T1

T2_light_deact

TIM-pp light deactivation

T2 > ∅

TIM_transl

TIM translation

∅ > T0

T_pho

TIM phosphorylation

T0 > T1

per_trans

per transkription

∅ > M_P

tim_trans

tim transkription

∅ > M_T

Parameters

Global parameters
CN_decay
C_decay
C_form
C_transp
M_P_decay
M_T_decay
P1_depho
P1_pho
P2_depho
P2_light_deact
PER_transl
P_pho
T1_depho
T1_pho
T2_depho
T2_light_deact
TIM_transl
T_pho
per_trans
tim_trans

Fixed species

Initial values

Functions and Rules

Assignment rules

v_dT = (1.0 + (v_dT_fac - 1.0) * ceil(sin(time / l_d * pi) * 0.9)) * v_dT_dark

Pt = P0 + P1 + P2 + C + CN * nucleus / cytoplasm

Tt = T0 + T1 + T2 + C + CN * nucleus / cytoplasm

Function definitions

Events

Constraints

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


Species:

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A model for circadian rhythms in Drosophila incorporating the formation of a complex between the PER and TIM proteins.

  • Jean-Christophe Leloup
  • Albert Goldbeter
J. Biol. Rhythms 1998; 13 (1): 70
Abstract
The authors present a model for circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The model for the circadian clock is based on multiple phosphorylation of PER and TIM and on the negative feedback exerted by a nuclear PER-TIM complex on the transcription of the per and tim genes. Periodic behavior occurs in a large domain of parameter space in the form of limit cycle oscillations. These sustained oscillations occur in conditions corresponding to continuous darkness or to entrainment by light-dark cycles and are in good agreement with experimental observations on the temporal variations of PER and TIM and of per and tim mRNAs. Birhythmicity (coexistence of two periodic regimes) and aperiodic oscillations (chaos) occur in a restricted range of parameter values. The results are compared to the predictions of a model based on the sole regulation by PER. Both the formation of a complex between PER and TIM and protein phosphorylation are found to favor oscillatory behavior. Determining how the period depends on several key parameters allows us to test possible molecular explanations proposed for the altered period in the per(l) and per(s) mutants. The extended model further allows the construction of phase-response curves based on the light-induced triggering of TIM degradation. These curves, established as a function of both the duration and magnitude of the effect of a light pulse, match the phase-response curves obtained experimentally in the wild type and per(s) mutant of Drosophila.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000171) Biomodels notes: The model has been simulated using copasi 4.3(build 25) For fig 4A one parameter, v_dT_fac, has been changed to 1 and the starting point of the simulation had to be changed to +32 hours to better fit the figure in the publication. JWS Online curation: This model was curated by reproducing Figure 4D.