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BIOMD0000000460 - Liebal2012 - B.subtilis sigB proteolysis model

 

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Reference Publication
Publication ID: 22511268
Liebal UW, Sappa PK, Millat T, Steil L, Homuth G, Völker U, Wolkenhauer O.
Proteolysis of beta-galactosidase following SigmaB activation in Bacillus subtilis.
Mol Biosyst 2012 Jun; 8(6): 1806-1814
Department of Systems Biology & Bioinformatics, University of Rostock, Rostock, Germany. ulf.liebal@uni-rostock.de  [more]
Model
Original Model: BIOMD0000000460.xml.origin
Submitter: Vijayalakshmi Chelliah
Submission ID: MODEL1302080000
Submission Date: 08 Feb 2013 13:03:02 UTC
Last Modification Date: 10 Jun 2013 13:46:42 UTC
Creation Date: 06 Jun 2013 19:30:32 UTC
Encoders:  Vijayalakshmi Chelliah
   Ulf Liebal
set #1
bqbiol:hasProperty Gene Ontology regulation of proteolysis
set #2
bqbiol:occursIn Taxonomy Bacillus subtilis
Notes
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.

Model
Publication ID: 22511268 Submission Date: 08 Feb 2013 13:03:02 UTC Last Modification Date: 10 Jun 2013 13:46:42 UTC Creation Date: 06 Jun 2013 19:30:32 UTC
Mathematical expressions
Reactions
v1 v2 v3  
Physical entities
Compartments Species
compartment IPTG sigb lacz
x    
Global parameters
kbd kbs kbx kxd
kxs kzd kzs  
Reactions (3)
 
 v1 [IPTG] ↔ [sigb];   {x} , {IPTG} , {sigb} , {x}
 
 v2 [sigb] ↔ [lacz];   {lacz} , {sigb}
 
 v3 [sigb] ↔ [x];   {sigb} , {x}
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0
 
 IPTG
Compartment: compartment
Initial concentration: 100.0
Constant
 
 sigb
Compartment: compartment
Initial concentration: 0.0
 
 lacz
Compartment: compartment
Initial concentration: 0.0
 
 x
Compartment: compartment
Initial concentration: 0.0
 
Global Parameters (7)
 
 kbd
Value: 5.8E-9
Constant
 
 kbs
Value: 100.0
Constant
 
 kbx
Value: 8.4E-5
Constant
 
 kxd
Value: 1.2E-13
Constant
 
 kxs
Value: 2.0E-6
Constant
 
 kzd
Value: 0.052
Constant
 
 kzs
Value: 1.7E-6
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000460

Curator's comment: (updated: 08 Feb 2013 13:24:14 GMT)

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).

Additional file(s)
  • Simulation experiment description::
    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/).
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