Liebal2012 - B.subtilis post-transcriptional instability model

Liebal2012 - B.subtilis post-transcription instability 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 post-transcription instability model (MODEL1302080001).

This model is described in the article:
Proteolysis of beta-galactosidase following SigmaB activation in Bacillus subtilis.

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).

This model is hosted on BioModels Database
and identified
by: MODEL1302080001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.

To the extent possible under law, all copyright and related or
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for more information.

Liebal2012——枯草芽孢杆菌（Bacillus subtilis）转录后不稳定模型

枯草芽孢杆菌的一类重要转录因子为σ因子B（Sigma B）。Liebal等人（2012年）以野生型与突变型B.subtilis菌株为实验对象，对σ因子B活性动力学的数学模型开展了验证实验。本次研究构建了三类模型，并测试其拟合实验数据的能力：1）转录抑制模型（MODEL1212180000）；2）σ因子B蛋白水解模型（MODEL1302080000）；3）转录后不稳定模型（Post-transcriptional instability model，MODEL1302080001）。本模型即对应上述转录后不稳定模型（MODEL1302080001）。

本模型载于下述学术文献：
《枯草芽孢杆菌σ(B)激活后β-半乳糖苷酶的蛋白水解过程》
作者：Liebal UW, Sappa PK, Millat T, Steil L, Homuth G, Völker U, Wolkenhauer O
发表信息：2012年6月；8(6):1806-14

摘要：
在B.subtilis中，σ(B)介导的普遍应激反应可帮助菌体抵御各类环境与能量相关应激条件。为深入解析普遍应激反应的调控机制，需明确各组分间的相互作用模式。本研究以野生型与突变型B.subtilis菌株为实验对象，对σ(B)活性动力学的数学模型开展验证实验。在突变菌株BSA115中，σ(B)的转录可通过添加IPTG诱导，且抗σ因子RsbW对σ(B)活性的负调控功能缺失。与预期中ctc::lacZ融合基因持续表达β-半乳糖苷酶的结果不同，本研究在该突变株中观测到了瞬时的酶活性。为解释这一实验现象，我们构建了数种反映σ(B)与β-半乳糖苷酶动力学调控假说的数学模型。仅当模型假设ctc::lacZ mRNA或β-半乳糖苷酶蛋白存在不稳定特性时，其仿真结果才能复现实验观测结果。后续的Northern印迹（Northern blot）实验显示，σ(B)应答诱导后，ctc::lacZ mRNA的浓度维持在稳定的高水平。因此我们推断，σ(B)激活后引发的蛋白不稳定特性，是解释本实验观测结果的最合理解释。本研究结果支持下述观点：B.subtilis在普遍应激反应激活后，可通过增强胞内蛋白水解降解能力，以适应环境挑战并调整蛋白质组构成。本研究结果同时对采用lacZ报告基因融合分析应激反应动力学的实验策略具有实践指导意义，该策略是σ(B)应答研究中的常用手段。

本研究复现了参考文献中的图3a，展示了不同IPTG浓度（100M、200M与1000M）下的β-半乳糖苷酶（模型中记为lacz）活性。本模型可使用SED-ML（仿真实验描述标记语言，Simulation Experiment Description Markup Language）文件进行操作（详见标注整理标签页）。

本模型托管于BioModels数据库（BioModels Database），编号为MODEL1302080001。
引用BioModels数据库的参考文献格式为：《BioModels数据库：面向已发表定量动力学模型的增强型标注注释资源》。

在法律允许的最大范围内，本编码模型的所有著作权及相关邻接权利已全部捐赠至全球范围公共领域。详细信息请参阅CC0公共领域贡献声明（CC0 Public Domain Dedication）。