From 2010.igem.org

Modeling of the chemotactic receptor 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 do many assumptions in order to suit the question of the investigation. It was therefore decided to implement four different models to be able to achieve a more general consensus prediction of chemotactic 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).

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 40 uM, anchor in a concentration of 50 uM. Medium asparate levels (10^-6 uM) were chosen.

Total Che protein species predicted by the model of Spiro et al. (1997)

Response of the system. CheYp amplitude is predicted to be high, according to the model of Spiro et al. (1997)

The model from Spiro et al. (1997) [1] has been adapted to identify candidates of the chemotactic 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 40 uM, anchor in a concentration of 50 uM. Medium asparate levels (10^-6 uM) were chosen.

Total Che protein species predicted by the model of Mello & Tu (2003).

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] [http://www.pnas.org/content/94/14/7263.full Spiro et al: A model of excitation and adaptation in bacterial chemotaxis. PNAS 1997 94;14;7263-7268.]

[2] [http://www.cell.com/biophysj/retrieve/pii/S0006349503700216 Mello & Tu: Perfect and Near-Perfect Adaptation in a Model of Bacterial Chemotaxis. Biophysical Journal 2003 84;5;2943-2956.]

[3] [http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020049 Rao et al: Design and Diversity in Bacterial Chemotaxis. PLoS Biol 2004;2;2;239-252.]

[4] [http://www.nature.com/nature/journal/v387/n6636/abs/387913a0.html Barkai & Leibler: Robustness in simple biochemical networks. Nature 1997;387;913-917.]