From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli
Background Bacteria have evolved a rich set of mechanisms for sensing and adapting to adverse conditions in their environment. These are crucial for their survival, which requires them to react to extracellular stresses such as heat shock, ethanol treatment or phage infection. Here we focus on st...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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BioMed Central Ltd.
2011
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| Online Access: | http://hdl.handle.net/1721.1/66984 |
| _version_ | 1826203345463803904 |
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| author | Toni, Tina Jovanovic, Goran Huvet, Maxime Buck, Martin Stumpf, Michael P. H. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Toni, Tina Jovanovic, Goran Huvet, Maxime Buck, Martin Stumpf, Michael P. H. |
| author_sort | Toni, Tina |
| collection | MIT |
| description | Background
Bacteria have evolved a rich set of mechanisms for sensing and adapting to adverse conditions in their environment. These are crucial for their survival, which requires them to react to extracellular stresses such as heat shock, ethanol treatment or phage infection. Here we focus on studying the phage shock protein (Psp) stress response in Escherichia coli induced by a phage infection or other damage to the bacterial membrane. This system has not yet been theoretically modelled or analysed in silico.
Results
We develop a model of the Psp response system, and illustrate how such models can be constructed and analyzed in light of available sparse and qualitative information in order to generate novel biological hypotheses about their dynamical behaviour. We analyze this model using tools from Petri-net theory and study its dynamical range that is consistent with currently available knowledge by conditioning model parameters on the available data in an approximate Bayesian computation (ABC) framework. Within this ABC approach we analyze stochastic and deterministic dynamics. This analysis allows us to identify different types of behaviour and these mechanistic insights can in turn be used to design new, more detailed and time-resolved experiments.
Conclusions
We have developed the first mechanistic model of the Psp response in E. coli. This model allows us to predict the possible qualitative stochastic and deterministic dynamic behaviours of key molecular players in the stress response. Our inferential approach can be applied to stress response and signalling systems more generally: in the ABC framework we can condition mathematical models on qualitative data in order to delimit e.g. parameter ranges or the qualitative system dynamics in light of available end-point or qualitative information. |
| first_indexed | 2024-09-23T12:35:08Z |
| format | Article |
| id | mit-1721.1/66984 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:35:08Z |
| publishDate | 2011 |
| publisher | BioMed Central Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/669842022-10-01T09:54:45Z From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli Toni, Tina Jovanovic, Goran Huvet, Maxime Buck, Martin Stumpf, Michael P. H. Massachusetts Institute of Technology. Department of Biological Engineering Toni, Tina Toni, Tina Background Bacteria have evolved a rich set of mechanisms for sensing and adapting to adverse conditions in their environment. These are crucial for their survival, which requires them to react to extracellular stresses such as heat shock, ethanol treatment or phage infection. Here we focus on studying the phage shock protein (Psp) stress response in Escherichia coli induced by a phage infection or other damage to the bacterial membrane. This system has not yet been theoretically modelled or analysed in silico. Results We develop a model of the Psp response system, and illustrate how such models can be constructed and analyzed in light of available sparse and qualitative information in order to generate novel biological hypotheses about their dynamical behaviour. We analyze this model using tools from Petri-net theory and study its dynamical range that is consistent with currently available knowledge by conditioning model parameters on the available data in an approximate Bayesian computation (ABC) framework. Within this ABC approach we analyze stochastic and deterministic dynamics. This analysis allows us to identify different types of behaviour and these mechanistic insights can in turn be used to design new, more detailed and time-resolved experiments. Conclusions We have developed the first mechanistic model of the Psp response in E. coli. This model allows us to predict the possible qualitative stochastic and deterministic dynamic behaviours of key molecular players in the stress response. Our inferential approach can be applied to stress response and signalling systems more generally: in the ABC framework we can condition mathematical models on qualitative data in order to delimit e.g. parameter ranges or the qualitative system dynamics in light of available end-point or qualitative information. Medical Research Council (Great Britain) Biotechnology and Biological Sciences Research Council (Great Britain) Wellcome Trust (London, England) Royal Society (Great Britain) (Wolfson Research Merit Award) 2011-11-09T21:15:46Z 2011-11-09T21:15:46Z 2011-05 2010-04 Article http://purl.org/eprint/type/JournalArticle 1752-0509 http://hdl.handle.net/1721.1/66984 Toni, Tina et al. “From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli.” BMC Systems Biology 5 (2011): 69. en_US http://dx.doi.org/10.1186/1752-0509-5-69 BMC Systems Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0/ application/pdf BioMed Central Ltd. BMC |
| spellingShingle | Toni, Tina Jovanovic, Goran Huvet, Maxime Buck, Martin Stumpf, Michael P. H. From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli |
| title | From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli |
| title_full | From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli |
| title_fullStr | From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli |
| title_full_unstemmed | From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli |
| title_short | From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli |
| title_sort | from qualitative data to quantitative models analysis of the phage shock protein stress response in escherichia coli |
| url | http://hdl.handle.net/1721.1/66984 |
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