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Ammonium assimilation model (AmtB transporter and protein level regulation)
Modelling is an important methodology in systems biology research. In this paper, we presented a kinetic model for the complex ammonium assimilation regulation system of E. coli. Based on a previously published model, the new model included the AmtB mediated ammonium transport and its protein level regulation by GlnK. Protein concentrations and several parameter values were determined or refined based on new experimental data. Steady-state analysis of the model showed that the expression of AmtB increased the ammonium assimilation rate by 4-5 fold at external ammonium concentrations as low as 5 µM. Model analysis also suggested that AmtB and GS levels were coupled to maximize the assimilation flux and to avoid a possible negative ammonia diffusion flux. In addition, model simulation of the short term dynamic response to increased external ammonium concentrations implied that the maximal rate for GlnB/GlnK uridylylation/deuridylylation should be higher for a quick response to environmental changes.

[ See and amtb-GS24.sbml]

Central carbon metabolic models

 A model of the phosphotransferase system (PTS) was constructed by Rohwer et al. and a model of glycolysis, pentose phosphate pathway and biosynthesis was constructed by Chassagnole et al. The two models are available on JWS online, a on-line repository. These two models were connected in a large kinetic model. This model will be available on JWS online after publication.

[ See link ]

Central nitrogen metabolic models

 A model of the central nitrogen assimilation network was constructed by Bruggeman et al. and this model is available on JWS online. The extended model of ammonium transport and assimilation will be available on JWS online soon.

[ See link ]

Qualitative model of network of global regulators in E. coli

The adaptation of the bacterium Escherichia coli to carbon starvation is controlled by a large network of biochemical reactions involving genes, mRNAs, proteins, and signalling molecules. The dynamics of these networks is difficult to analyze, notably due to a lack of quantitative information on parameter values. To overcome these limitations, model reduction approaches based on quasi-steady-state (QSS) and piecewise-linear (PL) approximations have been proposed, resulting in models that are easier to handle mathematically and computationally. These approximations are not supposed to affect the capability of the model to account for essential dynamical properties of the system, but the validity of this assumption has not been systematically tested. In this paper we carry out such a study by evaluating a large and complex PL model of the carbon starvation response in E. coli using an ensemble approach. The results show that, in comparison with conventional nonlinear models, the PL approximations generally preserve the dynamics of the carbon starvation response network, although with some deviations concerning notably the quantitative precision of the model predictions. This encourages the application of PL models to the qualitative analysis of bacterial regulatory networks, in situations where the reference time-scale is that of protein synthesis and degradation.

[ See link1, link2, ecoli.sbml, GNA basic and GNA extended ]