Liebal2012 - B.subtilis sigB proteolysis model

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Liebal2012 - B.subtilis sigB proteolysis model

An important transcription factor of B.subsilis is sigma B . Liebal et al. (2012) have performed experiments in B.subtilis wild type and mutant straits to test and validate a mathematical model of the dynamics of sigma B activity. The following three models were constructed and their ability to fit the experimental data were tested. 1) Transcription inhibition model (MODEL1212180000), 2) sigma B proteolysis model (MODEL1302080000) and 3) Post-transcriptional instability model (MODEL1302080001). This model corresponds to the sigma B proteolysis model (MODEL1302080000).

This model is described in the article:

Liebal UW, Sappa PK, Millat T, Steil L, Homuth G, Völker U, Wolkenhauer O.
2012 Jun;8(6):1806-14.

Abstract:

In Bacillus subtilis the σ(B) mediated general stress response provides protection against various environmental and energy related stress conditions. To better understand the general stress response, we need to explore the mechanism by which the components interact. Here, we performed experiments in B. subtilis wild type and mutant strains to test and validate a mathematical model of the dynamics of σ(B) activity. In the mutant strain BSA115, σ(B) transcription is inducible by the addition of IPTG and negative control of σ(B) activity by the anti-sigma factor RsbW is absent. In contrast to our expectations of a continuous β-galactosidase activity from a ctc::lacZ fusion, we observed a transient activity in the mutant. To explain this experimental finding, we constructed mathematical models reflecting different hypotheses regarding the regulation of σ(B) and β-galactosidase dynamics. Only the model assuming instability of either ctc::lacZ mRNA or β-galactosidase protein is able to reproduce the experiments in silico. Subsequent Northern blot experiments revealed stable high-level ctc::lacZ mRNA concentrations after the induction of the σ(B) response. Therefore, we conclude that protein instability following σ(B) activation is the most likely explanation for the experimental observations. Our results thus support the idea that B. subtilis increases the cytoplasmic proteolytic degradation to adapt the proteome in face of environmental challenges following activation of the general stress response. The findings also have practical implications for the analysis of stress response dynamics using lacZ reporter gene fusions, a frequently used strategy for the σ(B) response.

Figure 3a of the reference article has been reproduced. beta-galactosidase (lacz in model) activity at different concentrations of IPTG (100M, 200M and 1000M) has been reproduced. SED-ML (Simulation Experiment Description Markup Language) file is available for this model (see curation tab).

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Proteolysis of beta-galactosidase following SigmaB activation in Bacillus subtilis.
  • Liebal UW, Sappa PK, Millat T, Steil L, Homuth G, Völker U, Wolkenhauer O
  • Molecular bioSystems , 6/ 2012 , Volume 8 , pages: 1806-1814
  • Department of Systems Biology & Bioinformatics, University of Rostock, Rostock, Germany. ulf.liebal@uni-rostock.de
  • In Bacillus subtilis the σ(B) mediated general stress response provides protection against various environmental and energy related stress conditions. To better understand the general stress response, we need to explore the mechanism by which the components interact. Here, we performed experiments in B. subtilis wild type and mutant strains to test and validate a mathematical model of the dynamics of σ(B) activity. In the mutant strain BSA115, σ(B) transcription is inducible by the addition of IPTG and negative control of σ(B) activity by the anti-sigma factor RsbW is absent. In contrast to our expectations of a continuous β-galactosidase activity from a ctc::lacZ fusion, we observed a transient activity in the mutant. To explain this experimental finding, we constructed mathematical models reflecting different hypotheses regarding the regulation of σ(B) and β-galactosidase dynamics. Only the model assuming instability of either ctc::lacZ mRNA or β-galactosidase protein is able to reproduce the experiments in silico. Subsequent Northern blot experiments revealed stable high-level ctc::lacZ mRNA concentrations after the induction of the σ(B) response. Therefore, we conclude that protein instability following σ(B) activation is the most likely explanation for the experimental observations. Our results thus support the idea that B. subtilis increases the cytoplasmic proteolytic degradation to adapt the proteome in face of environmental challenges following activation of the general stress response. The findings also have practical implications for the analysis of stress response dynamics using lacZ reporter gene fusions, a frequently used strategy for the σ(B) response.
Contributors
administrator, Vijayalakshmi Chelliah

Metadata information

is
BioModels Database MODEL1302080000
BioModels Database BIOMD0000000460
isDescribedBy
PubMed 22511268
hasTaxon
hasProperty
Gene Ontology GO:0030162
Curation status
Curated
Name Description Size Actions

Model files

BIOMD0000000460_url.xml SBML L2V4 representation of Liebal2012 - B.subtilis sigB proteolysis model 18.66 KB Preview | Download

Additional files

BIOMD0000000460.xpp Auto-generated XPP file 1.64 KB Preview | Download
BIOMD0000000460.m Auto-generated Octave file 3.34 KB Preview | Download
BIOMD0000000460-biopax2.owl Auto-generated BioPAX (Level 2) 9.12 KB Preview | Download
BIOMD0000000460-SEDML.xml This SED-ML file can be used to reproduce the curation result (for example, figure 3b of the reference publication), by loading it into SED-ML Web Tools (http://sysbioapps.dyndns.org/SED-ML_Web_Tools/). 4.27 KB Preview | Download
BIOMD0000000460.sci Auto-generated Scilab file 1.29 KB Preview | Download
BIOMD0000000460_urn.xml Auto-generated SBML file with URNs 20.24 KB Preview | Download
BIOMD0000000460.vcml Auto-generated VCML file 910.00 bytes Preview | Download
BIOMD0000000460-biopax3.owl Auto-generated BioPAX (Level 3) 11.72 KB Preview | Download
BIOMD0000000460.png Auto-generated Reaction graph (PNG) 39.83 KB Preview | Download
BIOMD0000000460.pdf Auto-generated PDF file 147.11 KB Preview | Download
BIOMD0000000460.svg Auto-generated Reaction graph (SVG) 10.39 KB Preview | Download

  • Model originally submitted by : administrator
  • Submitted: Feb 8, 2013 1:03:02 PM
  • Last Modified: Dec 21, 2018 5:18:56 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:18:56 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: BIOMD0000000460-SEDML.xml
  • Version: 2 public model Download this version
    • Submitted on: Jun 10, 2013 2:46:42 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Current version of Liebal2012 - B.subtilis sigB proteolysis model
  • Version: 1 public model Download this version
    • Submitted on: Feb 8, 2013 1:03:02 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Original import of Liebal2012 - B.subtilis sigB proteolysis model
Curator's comment:
(added: 08 Feb 2013, 13:24:14, updated: 08 Feb 2013, 13:24:14)
Figure 3b of the reference publication has been reproduced. Beta-galactosidase (lacz) activity at different values of IPTG (100M, 200M and 1000M) is observed in plot. The SED-ML file for this corresponding simulation can be downloaded (see below).