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veening1

veening1

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AprEdeg

AprE > ∅

AprEsyn

∅ > AprE

DimerAss

{2.0}DegUP > Dim

DimerDis

Dim > {2.0}DegUP

degradation1

DegU > ∅

degradation2

DegUP > ∅

degradation3

Dim > ∅

degradationmRNA

mDegU > ∅

dephosphorylation

DegUP > DegU

mRNAAprEdeg

mAprE > ∅

mRNAAprEsyn

∅ > mAprE

phosphorylation

DegU > DegUP

synthesisDegU

∅ > DegU

synthesismRNA

∅ > mDegU

Parameters

Global parameters

Fixed species

Initial values

Functions and Rules

Assignment rules

DegU_Total = DegU + DegUP + 2.0 * Dim

kdephos = q / ratio

kphos = ratio * p

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.


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log scales

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x-axis min/max

Transient heterogeneity in extracellular protease production by Bacillus subtilis.

  • Jan-Willem Veening
  • Oleg A Igoshin
  • Robyn T Eijlander
  • Reindert Nijland
  • Leendert W Hamoen
  • Oscar P Kuipers
Mol. Syst. Biol. 2008; 4 : 184
Abstract
The most sophisticated survival strategy Bacillus subtilis employs is the differentiation of a subpopulation of cells into highly resistant endospores. To examine the expression patterns of non-sporulating cells within heterogeneous populations, we used buoyant density centrifugation to separate vegetative cells from endospore-containing cells and compared the transcriptome profiles of both subpopulations. This demonstrated the differential expression of various regulons. Subsequent single-cell analyses using promoter-gfp fusions confirmed our microarray results. Surprisingly, only part of the vegetative subpopulation highly and transiently expresses genes encoding the extracellular proteases Bpr (bacillopeptidase) and AprE (subtilisin), both of which are under the control of the DegU transcriptional regulator. As these proteases and their degradation products freely diffuse within the liquid growth medium, all cells within the clonal population are expected to benefit from their activities, suggesting that B. subtilis employs cooperative or even altruistic behavior. To unravel the mechanisms by which protease production heterogeneity within the non-sporulating subpopulation is established, we performed a series of genetic experiments combined with mathematical modeling. Simulations with our model yield valuable insights into how population heterogeneity may arise by the relatively long and variable response times within the DegU autoactivating pathway.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000240) Biomodels notes: Figure 7A and 7B is reproduced here. We got the following useful information for curation from the authors. In the paper, the x-axis is mislabelled by a factor of 5, and also the values for 3 of the parameters are incorrect in the paper. The parameters and their correct values are 1) Kdim (K1 for aprE, in the paper)= 12, 2) kphos (kph, in the paper) = 0.004, and 3) kdephos (kdeph, in the paper) = 0.15. All these are implemented in the model. The model was simulated and integrated using Copasi JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.