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Team:ETHZ Basel/Modeling/Combined
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= Combined Model = | = Combined Model = | ||
| - | [[Image:ETHZ_Basel_molecular.png|thumb|400px|'''Combined model.''' Coupled individual models for the simulation of the | + | [[Image:ETHZ_Basel_molecular.png|thumb|400px|'''Combined model.''' Coupled individual models for the simulation of the entire process and their interfaces. The concentration of CheYp determines the movement bias.]] |
== Interface == | == Interface == | ||
| - | To | + | To create the complete model of E. lemming, the individual modules [[Team:ETHZ_Basel/Modeling/Chemotaxis| chemotaxis pathway]], [[Team:ETHZ_Basel/Modeling/Light_switch| light switch]] and [[Team:ETHZ_Basel/Modeling/Movement| movement model]] were coupled, by defining input - output interfaces. The combination was achieved in two steps: |
* First, the deterministic light switch and chemotaxis models were combined by assuming a complete removal of a selected Che protein species by the light switch. The interface was defined as the concentration ([LSP-Che]) of this linked device. | * First, the deterministic light switch and chemotaxis models were combined by assuming a complete removal of a selected Che protein species by the light switch. The interface was defined as the concentration ([LSP-Che]) of this linked device. | ||
| - | * Second, the stochastic movement model was combined with the light switch - chemotaxis model. The | + | * Second, the stochastic movement model was combined with the light switch - chemotaxis model. The interface was defined as the dependency CheYp - directed movement probability (or the bias). At every time point of the simulation, the next state (directed movement/tumbling) of the bacterium was selected, based on the value of the input bias. |
| - | [[Image:ETHZ_Basel_models_overview_comb.png|thumb|400px|'''Combined model.''' Coupled individual models for the simulation of the | + | [[Image:ETHZ_Basel_models_overview_comb.png|thumb|400px|'''Combined model.''' Coupled individual models for the simulation of the entire process and their interfaces.]] |
== Light switch - Chemotaxis == | == Light switch - Chemotaxis == | ||
| - | [[Image:ETHZ_Basel_chemotactical_network.png|thumb|400px|'''Schematical overview on the chemotactical pathway.''' MCPs refers to the membrane receptor proteins and Che are the intracellular | + | [[Image:ETHZ_Basel_chemotactical_network.png|thumb|400px|'''Schematical overview on the chemotactical pathway.''' MCPs refers to the membrane receptor proteins and Che are the intracellular proteins of the chemotaxis pathway.]] |
The following assumptions have been made according to the [[Team:ETHZ_Basel/Biology/Molecular_Mechanism| molecular mechanism]] to link the light switch and chemotaxis models: | The following assumptions have been made according to the [[Team:ETHZ_Basel/Biology/Molecular_Mechanism| molecular mechanism]] to link the light switch and chemotaxis models: | ||
| - | Upon red light pulse induction, the two light-sensitive proteins dimerize and thus the coupled Che protein is spatially dislocated. This means | + | * Upon red light pulse induction, the two light-sensitive proteins dimerize and thus the coupled Che protein is spatially dislocated. This means |
| - | * CheR is not able to methylate the MCPs anymore, | + | ** CheR is not able to methylate the MCPs anymore, |
| - | * CheY can't be phosphorylated and interact with the motor anymore; nevertheless, it still can be dephosphorylated. | + | ** CheY can't be phosphorylated and interact with the motor anymore; nevertheless, it still can be dephosphorylated. |
| - | Since CheB and CheZ regulate the chemotactic receptor pathway inverse compared to CheR and CheY, they repress tumbling | + | * Since CheB and CheZ regulate the chemotactic receptor pathway inverse compared to CheR and CheY, they repress tumbling |
| - | * CheB is not able to demethylate the MCPs and can't be phosphorylated anymore, but still can be dephosphorylated, | + | ** CheB is not able to demethylate the MCPs and can't be phosphorylated anymore, but still can be dephosphorylated, |
| - | * CheZ can't dephosphorylate CheY anymore (This assumption is very unsteady, since CheY is not strictly located). | + | ** CheZ can't dephosphorylate CheY anymore (This assumption is very unsteady, since CheY is not strictly located). |
All of these assumptions will lead to a decrease of tumbling / directed movement ratio upon red light induction and an increase of corresponding far-red light induction. | All of these assumptions will lead to a decrease of tumbling / directed movement ratio upon red light induction and an increase of corresponding far-red light induction. | ||
== Chemotaxis - Movement == | == Chemotaxis - Movement == | ||
| - | The combination of the deterministic and probabilistic models was (first) the biggest challenge and (afterwards) the biggest accomplishment in combining the models. Besides its theoretical complexity, the complete coupling is also conceptually very important. It closes the loop of our modeling and it combines two different types of models: deterministic and | + | The combination of the deterministic and probabilistic models was (first) the biggest challenge and (afterwards) the biggest accomplishment in combining the models. Besides its theoretical complexity, the complete coupling is also conceptually very important. It closes the loop of our E. lemming modeling and it combines two different types of models: deterministic and stochastic, under the same global approach. |
<br> | <br> | ||
The two models have different timesteps, the molecular one being much faster than the stochastic one, therefore their combination has been done via Simulink interface. Both models have been independently numerically integrated and the output of the deterministic model was passed as an input to the stochastic one, at every slower time-step. | The two models have different timesteps, the molecular one being much faster than the stochastic one, therefore their combination has been done via Simulink interface. Both models have been independently numerically integrated and the output of the deterministic model was passed as an input to the stochastic one, at every slower time-step. | ||
<br> | <br> | ||
The main assumption we used in the complete coupling was that the mean run length is a function of the bias, while mean tumbling length is bias - independent. | The main assumption we used in the complete coupling was that the mean run length is a function of the bias, while mean tumbling length is bias - independent. | ||
Revision as of 14:57, 25 October 2010
Combined Model
Interface
To create the complete model of E. lemming, the individual modules chemotaxis pathway, light switch and movement model were coupled, by defining input - output interfaces. The combination was achieved in two steps:
- First, the deterministic light switch and chemotaxis models were combined by assuming a complete removal of a selected Che protein species by the light switch. The interface was defined as the concentration ([LSP-Che]) of this linked device.
- Second, the stochastic movement model was combined with the light switch - chemotaxis model. The interface was defined as the dependency CheYp - directed movement probability (or the bias). At every time point of the simulation, the next state (directed movement/tumbling) of the bacterium was selected, based on the value of the input bias.
Light switch - Chemotaxis
The following assumptions have been made according to the molecular mechanism to link the light switch and chemotaxis models:
- Upon red light pulse induction, the two light-sensitive proteins dimerize and thus the coupled Che protein is spatially dislocated. This means
- CheR is not able to methylate the MCPs anymore,
- CheY can't be phosphorylated and interact with the motor anymore; nevertheless, it still can be dephosphorylated.
- Since CheB and CheZ regulate the chemotactic receptor pathway inverse compared to CheR and CheY, they repress tumbling
- CheB is not able to demethylate the MCPs and can't be phosphorylated anymore, but still can be dephosphorylated,
- CheZ can't dephosphorylate CheY anymore (This assumption is very unsteady, since CheY is not strictly located).
All of these assumptions will lead to a decrease of tumbling / directed movement ratio upon red light induction and an increase of corresponding far-red light induction.
Chemotaxis - Movement
The combination of the deterministic and probabilistic models was (first) the biggest challenge and (afterwards) the biggest accomplishment in combining the models. Besides its theoretical complexity, the complete coupling is also conceptually very important. It closes the loop of our E. lemming modeling and it combines two different types of models: deterministic and stochastic, under the same global approach.
The two models have different timesteps, the molecular one being much faster than the stochastic one, therefore their combination has been done via Simulink interface. Both models have been independently numerically integrated and the output of the deterministic model was passed as an input to the stochastic one, at every slower time-step.
The main assumption we used in the complete coupling was that the mean run length is a function of the bias, while mean tumbling length is bias - independent.
