Team:ETHZ Basel/Modeling

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= Molecular Modeling Overview =
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= Mathematical Modeling Overview =
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[[Image:ETHZ_Basel_molecular_comb.png|thumb|400px|'''Schematical overview of the devices and change upon light pulse induction.''' LSP refers to light switch protein, AP to anchor protein, anchor to the plasmid anchor 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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In order to support [[Team:ETHZ_Basel/Biology|wet laboratory experiments]] and to create a test bench for the [[Team:ETHZ_Basel/InformationProcessing|information processing]] part, a molecular model of E. lemming was created. This goal was achieved by implementing and combining deterministic and probabilistic molecular models of the individual parts.
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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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The core component of E. lemming is the fusion of one light-sensitive protein (LSP1) to a protein of the chemotaxis pathway (Che). Upon change of wavelength of light pulses, this component will dimerize with the corresponding light-sensitive protein (LSP2), which is linked to an anchor protein, bound to an anchor (plasmid). The result is a change of the spatial localization of Che and perturbation of the chemotaxis pathway, which ultimately leads to a different tumbling/directed movement state ratio.
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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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== Implementation of molecular models ==
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* [[Team:ETHZ_Basel/Modeling/Light_Switch|'''Light Switch''']]: both implementation approaches have been modeled:
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=== Individual molecular models ===
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** [[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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In a first step, we implemented individual molecular models of subdevices.
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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.
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* [[Team:ETHZ_Basel/Modeling/Light_Switch|'''Light Switch''']]: based upon the light-sensitive dimerizing Arabidopsis proteins PhyB and PIF3.
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* [[Team:ETHZ_Basel/Modeling/Chemotaxis|'''Chemotaxis Pathway''']]: two deterministic molecular models of the chemotaxis pathway.
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* [[Team:ETHZ_Basel/Modeling/Chemotaxis|'''Chemotaxis''']]: two similar models of the chemotactic receptor pathway.
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* [[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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* [[Team:ETHZ_Basel/Modeling/Movement|'''Movement''']]: a probabilistic model of E. coli movement, determined by distribution of input bias.
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=== Combined molecular 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 whole 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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The next step, combination of the individual molecular models to a comprehensive model of E. lemming was achieved in two substeps:
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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''']]: used to provide support for wet laboratory.
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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 |''' Chemotaxis - Movement''']]: complete molecular model.
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== Collaboration with wet laboratory and information processing ==
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=== Evaluation for wet laboratory ===
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To create the biological implementation of E. lemming, the parts of the core components had to be chosen in an order to improve chances to result in a functioning ensemble. By using the combined molecular models for ''in silico'' evaluation of the best possible parts, it was possible to reduce the amount of different combinations to be tested.
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[[Team:ETHZ_Basel/Modeling/Collaboration|''' Wet laboratory evaluation results''']] have showed, that molecular modeling and experimental biology can collaborate to gain new insight for both perceptions of the problem.
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=== Evaluation 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/Collaboration|'''Information processing evaluation results''']] provide further information how this 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 molecular models have been used to create and evaluate the controller. By providing an input port for light pulse and an output port for movement, it was possible to close the loop and simulate the whole system.
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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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