Team:ETHZ Basel/Modeling

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(Mathematical Modeling Overview)
 
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= Molecular Modeling Overview =
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= Mathematical Modeling Overview =
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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 molecular models of the individual parts.
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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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== Implementation of molecular models ==
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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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[[Image:Modeling_overview.png|thumb|400px|'''Combined models.''' Coupled individual models for the simulation of the whole process and their interfaces.]]
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The core component of E. lemming is the fusion of one light-sensitive protein (LSP?) 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 (LSP?'), 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/straight run 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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E. lemming, aims to modify the chemotaxis property of E.coli such that, instead of response to a chemical attractant or repellent, the bacterium responds to a light stimulus. Furthermore, this light sensitivity is used to control E.coli’s movement by deciding, at any given time, which type of motion the bacterium will adopt (tumbling or straight run). This leads to a controllable E.coli, which can move to a defined direction, as a result of the combination of tumbling and straight run. The bacteria in the experiment are imaged and, by image processing, the position of a single tracked cell is inferred. By activating a light switch, the user decides whether the bacterium should continue running or should change direction.
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* [[Team:ETHZ_Basel/Modeling/Light_Switch|'''Light Switch''']]: both implementation approaches have been modeled:
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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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** [[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/Chemotaxis|'''Chemotaxis Pathway''']]: two deterministic molecular models of the chemotaxis 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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In the theory world, the steps we are following in mindlessly driving E.coli to our pre - defined target are the following:
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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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* [[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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• deterministic (ODE) & stochastic models of the chemotaxis pathway (documented from the literature)<br>
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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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• model of the movement of E.coli (built on the information of the pathway derived from the molecular models) <br> 
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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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• control algorithms ( built on the user’s desire to play around with E.coli)<br>
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• image tracking & image processing algorithms<br>
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• java applications/movies of the E.Lemming (the fun part)<br>
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== Support for wet laboratory ==
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== Test bench for information processing ==
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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: