Team:ETHZ Basel/Modeling

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= Mathematical Modeling Overview =
= Mathematical Modeling Overview =
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[[Image:ETHZ_Basel_molecular_comb.png|thumb|400px|'''Schematical overview of the modeled processes in E. lemming.''' LSP refers to light switch protein, AP to anchor protein, and Che to the attacked protein of the chemotaxis pathway.]]
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[[Image:ETHZ_Basel_molecular_comb.png|thumb|400px|'''Figure 1: schematical overview of the modeled processes in E. lemming.''' LSP refers to light switch protein, AP to anchor protein, and Che to the attacked protein of the chemotaxis pathway.]]
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A complex mathematical model of E. lemming from both literature inspired and self developed submodels was created. The final implementation combines deterministic molecular models of the [[Team:ETHZ_Basel/Modeling/Chemotaxis| chemotaxis pathway]], the [[Team:ETHZ_Basel/Modeling/Light_Switch| light switch]] and a probabilistic model for the [[Team:ETHZ_Basel/Modeling/Movement| bacterial movement]] in one model.
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A complex mathematical model of E. lemming from both literature inspired and self developed submodels was created that covers the processes displayed in Figure 1.
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This model was used to reduce [[Team:ETHZ_Basel/Biology|wet laboratory experiments]] by identify molecular targets and to create a simulative test bench for the [[Team:ETHZ_Basel/InformationProcessing|information processing]] algorithms.
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In a first step, existing models for the individual processes of E. lemming have been identified by literature research, implemented, corrected and adapted to our needs. Where we could not rely on established models, we started modeling on our own and calibrated the model with regard to available literature knowledge.
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== Model implementation ==
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=== Submodels ===
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In a first step, submodels for the individual processes of E. lemming have been identified by literature research, implemented, corrected and adapted to our needs. Where we could not rely on established models, we started modeling on our own and calibrating the model with regard to literature knowledge.
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* [[Team:ETHZ_Basel/Modeling/Light_Switch|'''Light Switch''']]: both implementation approaches have been modeled:
* [[Team:ETHZ_Basel/Modeling/Light_Switch|'''Light Switch''']]: both implementation approaches have been modeled:
** [[Team:ETHZ_Basel/Modeling/Light_Switch#Modeling_of_the_light_switch:_PhyB.2FPIF3|'''PhyB/PIF3''']]: a deterministic molecular model based on the light-sensitive dimerizing Arabidopsis proteins PhyB and PIF3.
** [[Team:ETHZ_Basel/Modeling/Light_Switch#Modeling_of_the_light_switch:_PhyB.2FPIF3|'''PhyB/PIF3''']]: a deterministic molecular model based on the light-sensitive dimerizing Arabidopsis proteins PhyB and PIF3.
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** [[Team:ETHZ_Basel/Modeling/Light_Switch#Modeling_of_the_light_switch:_Archeal_light_receptor|'''Archeal Light Receptor''']]: a deterministic molecular model based on the archeal light receptor.
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** [[Team:ETHZ_Basel/Modeling/Light_Switch#Modeling_of_the_PhyB.2FPIF3_light_switch#Archeal_light_receptor|'''Archeal Light Receptor''']]: a deterministic molecular model based on the archeal light receptor.
* [[Team:ETHZ_Basel/Modeling/Chemotaxis|'''Chemotaxis Pathway''']]: two deterministic molecular models of the chemotaxis pathway.
* [[Team:ETHZ_Basel/Modeling/Chemotaxis|'''Chemotaxis Pathway''']]: two deterministic molecular models of the chemotaxis pathway.
* [[Team:ETHZ_Basel/Modeling/Movement|'''Bacterial Movement''']]: a self developed stochastic model of ''E. coli'' movement on basis of the CheYp bias.
* [[Team:ETHZ_Basel/Modeling/Movement|'''Bacterial Movement''']]: a self developed stochastic model of ''E. coli'' movement on basis of the CheYp bias.
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=== Merged models ===
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In a second part, we combined the submodels stepwise to more comprehensive models that we could use to address different important questions to:  
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[[Image:ETHZ_Basel_models_overview_comb.png|thumb|400px|'''Combined models.''' Coupled individual models for the simulation of the entire process and their interfaces.]]
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* [[Team:ETHZ_Basel/Modeling/Combined#PhyB.2FPIF3_light_switch_-_Chemotaxis |'''PhyB/PIF3 light switch - Chemotaxis''']]: this model was used to reduce [[Team:ETHZ_Basel/Biology|wet laboratory experiments]] by identification molecular targets by [[Team:ETHZ_Basel/Modeling/Experimental_Design|experimental design]].
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Secondly we combined the submodels stepwise to more comprehensive models that we could use to address different important questions to:  
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* [[Team:ETHZ_Basel/Modeling/Combined#Archeal_light_receptor_-_Chemotaxis |'''Archeal light receptor - Chemotaxis''']]: this model was combined identically to the one above.
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* [[Team:ETHZ_Basel/Modeling/Combined#Light_switch_-_Chemotaxis |'''Light switch - Chemotaxis''']]: used for design of experiment for the biology lab and the information processing.
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* [[Team:ETHZ_Basel/Modeling/Combined#Chemotaxis_-_Movement |'''Chemotaxis - Movement''']]: complete model of E. lemming as a simulative test bench for the [[Team:ETHZ_Basel/InformationProcessing/Controller|controller]] design and as a brick of the comprehensive simulation of [[Team:ETHZ_Basel/InformationProcessing|information processing]].
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* [[Team:ETHZ_Basel/Modeling/Combined#Light_switch_-_Chemotaxis_-_Movement |'''Light switch - Chemotaxis - Movement''']]: complete model of E. lemming as a test bench for the controller design and a brick of the full simulation of information processing.
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== Experimental Design ==
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=== Insights for wet laboratory ===
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Since the design of E.lemming implies the existence of many possible biological combinations of the fundamental parts, the first steps in the modeling of our system were directed towards reducing the actual number of combinations implemented in the wetlab. Furthermore, by using the combined molecular models for ''in silico'' evaluation of the best possible devices, we derived theoretical results on choosing the biological parts which maximize the chance of a functional final ensemble.
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[[Team:ETHZ_Basel/Modeling/Experimental_Design#Insights_for_wet_laboratory|''' Wet laboratory evaluation results''']] have showed that molecular modeling and experimental biology can interwork to gain new insight on both aspects of our project.  
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=== Insights for information processing ===
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In order to adjust the controller to have optimal light pulse rates, the combined molecular model has been used to determine the corresponding time constants.
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[[Team:ETHZ_Basel/Modeling/Experimental_Design#Insights_for_information_processing|'''Information processing evaluation results''']] provide further information on how this task has been accomplished.
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== Test bench for information processing ==
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[[Image:ETHZ_Basel_models_overview_ip.png|thumb|400px|'''Test bench for information processing.''']]
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In order to create a first test bench for the information processing pipeline, the combined model has been used to set up and evaluate [[Team:ETHZ_Basel/InformationProcessing/Controller| the controller]].
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By providing input ports for the actual and the desired movement direction of the bacterium and boolean output ports for both light pulses (red light/far red light), it was possible to time - dependently control the E. lemming and close the loop in simulating the overall network.
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Latest revision as of 19:09, 27 October 2010

Mathematical Modeling Overview

Figure 1: schematical overview of the modeled processes in E. lemming. LSP refers to light switch protein, AP to anchor protein, and Che to the attacked protein of the chemotaxis pathway.

A complex mathematical model of E. lemming from both literature inspired and self developed submodels was created that covers the processes displayed in Figure 1.

In a first step, existing models for the individual processes of E. lemming have been identified by literature research, implemented, corrected and adapted to our needs. Where we could not rely on established models, we started modeling on our own and calibrated the model with regard to available literature knowledge.

  • Light Switch: both implementation approaches have been modeled:
    • PhyB/PIF3: a deterministic molecular model based on the light-sensitive dimerizing Arabidopsis proteins PhyB and PIF3.
    • Archeal Light Receptor: a deterministic molecular model based on the archeal light receptor.
  • Chemotaxis Pathway: two deterministic molecular models of the chemotaxis pathway.
  • Bacterial Movement: a self developed stochastic model of E. coli movement on basis of the CheYp bias.

In a second part, we combined the submodels stepwise to more comprehensive models that we could use to address different important questions to:

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