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elowitz1

elowitz1

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degradation of LacI transcripts

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transcription of LacI

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transcription of TetR

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transcription of CI

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translation of LacI

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Parameters

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Functions and Rules

Assignment rules

alpha0 = a0_tr * eff * tau_prot / (log(2.0) * KM)

alpha = a_tr * eff * tau_prot / (log(2.0) * KM)

kd_mRNA = log(2.0) / tau_mRNA

kd_prot = log(2.0) / tau_prot

a0_tr = ps_0 * 60.0

a_tr = (ps_a - ps_0) * 60.0

k_tl = eff / t_ave

beta = tau_mRNA / tau_prot

t_ave = tau_mRNA / log(2.0)

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


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A synthetic oscillatory network of transcriptional regulators.

  • Michael Elowitz
  • Stanislas Leibler
Nature 2000; 403 (6767): 335-338
Abstract
Networks of interacting biomolecules carry out many essential functions in living cells, but the 'design principles' underlying the functioning of such intracellular networks remain poorly understood, despite intensive efforts including quantitative analysis of relatively simple systems. Here we present a complementary approach to this problem: the design and construction of a synthetic network to implement a particular function. We used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli. The network periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells. The resulting oscillations, with typical periods of hours, are slower than the cell-division cycle, so the state of the oscillator has to be transmitted from generation to generation. This artificial clock displays noisy behaviour, possibly because of stochastic fluctuations of its components. Such 'rational network design may lead both to the engineering of new cellular behaviours and to an improved understanding of naturally occurring networks.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000012) Biomodels notes: This model describes the deterministic version of the repressilator system. To reproduce the simulations run published by the authors, the model has to be simulated with any of two different approaches. First, one could use a deterministic method ( KISAO_0000035 ) with continuous variables ( KISAO_0000018 ). One sample algorithm to use is the CVODE solver ( KISAO_0000019 ). Second, one could simulate the system using Gillespie's direct method ( KISAO_0000029 ), which is a stochastic method ( KISAO_0000036 ) supporting adaptive timesteps ( KISAO_0000041 ) and using discrete variables ( KISAO_0000016 ). See Biomodels Database for more information (http://www.ebi.ac.uk/biomodels-main/BIOMD0000000012). JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.