Team:ETHZ Basel/Modeling/Chemotaxis

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Modeling of the chemotaxis pathway

Schematical overview of the light switch device and the interaction with the chemotaxis pathway. LSP refers to light switch protein, AP to anchor protein and Che to the attacked protein of the chemotaxis pathway.

The chemotactic receptor pathway in E. coli is quite complex. Published models of chemotaxis [1], [2], [3], [4] thus have to use many assumptions in order to answer the investigated question. It was therefore decided to implement four different models to be able to achieve a more general consensus prediction of the chemotaxis behavior in E. lemming.

For the combined model implementation, only two chemotaxis models have been further investigated: Spiro et al. (1997) and Mello & Tu (2003).

The main importance of modeling the chemotaxis network lies in the fact that its output serves as an input for the Movement model and it represents the central decision factor in the spatial behavior of the bacterium.

Spiro et al. (1997) [1]

Che protein species predicted by the model of Spiro et al. (1997) CheY is coupled to PIF3. PhyB is present in a concentration of 100 uM, anchor in a concentration of 130 uM. Medium asparate levels (10^-6 uM) were chosen.
Total Che protein species predicted by the model of Spiro et al. (1997) Only the total concentration of CheY is changed by the light switch in this model.
Response of the system. CheYp amplitude is predicted to be high, according to the model of Spiro et al. (1997)

The model of Spiro et al. (1997) [1] has been adapted to identify candidates of the chemotaxis receptor pathway by enabling removal of a species upon light-induction. It basically predicts that all Che proteins (CheR, B, Y and Z) would be a suitable candidate. For CheR and CheY, the concentration of CheYp drops more than Delta (initial value - threshold), for CheB and CheZ it increases more than Delta. For all Che proteins, the concentrations stay below/above the threshold, until they are deactivated with far-red light. The best results were obtained for assuming a high ligand concentration (saturation, the methylation level of the receptors is high). For CheY and CheZ the reaction times were much faster than for CheB and CheR.

Mello & Tu (2003) [2]

Che protein species predicted by the model of Mello & Tu (2003) CheY is coupled to PIF3. PhyB is present in a concentration of 100 uM, anchor in a concentration of 130 uM. Medium asparate levels (10^-6 uM) were chosen.
Total Che protein species predicted by the model of Mello & Tu (2003). The total concentration of CheR is changed in addition to the CheYp concentration in this model
Response of the system. The model of Mello & Tu (2003) predicts a much smaller CheYp amplitude than the model of Spiro et al. (1997)

The model of Mello & Tu (2003) differs from Spiro et al. (1997) in a way, that it is able to reach perfect and near-perfect adaptation. They investigated robustness of this system, which covers the effect of attractant binding through the phosphorylation of CheY. Governing ODEs are derived by applying the law of mass action to the known reactions. Five states of methylation and demethylation of the attractant-bound and free receptors are considered. The Mello & Tu (2003) model has been adapted to support our approach and shows similar behavior compared to the adapted Spiro et al. (1997) model.

References

[1] Spiro et al: A model of excitation and adaptation in bacterial chemotaxis. PNAS 1997 94;14;7263-7268.

[2] Mello & Tu: Perfect and Near-Perfect Adaptation in a Model of Bacterial Chemotaxis. Biophysical Journal 2003 84;5;2943-2956.

[3] Rao et al: Design and Diversity in Bacterial Chemotaxis. PLoS Biol 2004;2;2;239-252.

[4] Barkai & Leibler: Robustness in simple biochemical networks. Nature 1997;387;913-917.