Team:TU Delft-Leiden/Modeling

From 2014.igem.org

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<h2> Modeling Overview</h2>
<h2> Modeling Overview</h2>
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<p>We developed models for each of the three different modules of our project: the <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Curli">conductive curli module</a>, the <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/EET">extracellular electron transport (EET) module</a> and the <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine">landmine detection module</a>. <br>
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For the conductive curli module, we wanted to know if a conductive path between two electrodes of a chip filled with curli growing <i> E. coli </i> arise at a certain point in time. We also wanted to make quantitative predictions about the resistance between the two electrodes of our system in time. <br>
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For the EET module, our goal was to investigate the carbon metabolism providing the electrons for the EET module. Also, we want the EET pathway used by the cells in order to have a measurable electrical signal for our biosensor, see the <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Gadget">gadget section</a> of our wiki. Furthermore, in our modeling of the assembly of the EET complex, we wanted to predict how many EET complexes are formed under different initial conditions. We focused, in addition to the assembly mechanism, also on the apparent reduced cell viability.<br>
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For the landmine module, we tried to find a model which would be able to reproduce the response curves of both the landmine promoters, as found in [1]. <br>
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For the EET and landmine modules, we used deterministic modeling. For the curli module, we used a stochastic modeling approach, and considered the system at the gene, cell and colony level. At the colony levvel, we employed <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Techniques#PercolationTheory">percolation theory</a> in order to predict if a conductive path between the two electrodes arise at a certain point in time and to predict at which time this happens. Our application of percolation theory to describe the formation of a conductive biological network represents a novel approach that has not been used in the literature before.
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</p>
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<p> We modeled all three different modules our project consists of, namely the landmine module, the Extracellular Electron Transport (EET) module and the conductive curli module. In order to achieve this, we had to use all kinds of different modeling methods.</p>
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<br>
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<p>
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We used Matlab for most of the calculations; the scripts we made can be found in the <a href="/Team:TU_Delft-Leiden/Modeling/CodeRepository">Code Repository</a>. We had great interactions with the Life Science and Microfluidics departments, which for the conductive curli module can be read <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Life_science/curli/integration">here</a>, for the EET module can be read <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Life_science/EET/integration">here</a> and for the landmine detection module can be read <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Life_science/landmine/integration">here</a>.  
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</p>
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<ul>
<ul>
      
      
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     <li>
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          <a href="/Team:TU_Delft-Leiden/Modeling/Landmine">
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        <a href="/Team:TU_Delft-Leiden/Modeling/Curli">
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          <p>Landmine Module</p>
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        <p>Curli Module</p>
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          </a>
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        </a>
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              <ul>
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          <ul>
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                    <li>
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              <li>
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Curli/Gene">
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine#simplemodel">
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                     <p>Gene Level Modeling</p>
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                     <p>Simple Binding Model </p>
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                     </a>
                     </a>
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              </li>
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              <li>
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                    </li>
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine#coopbinding">
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                     <p>Cooperative Binding Model</p>
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                    <li>
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Curli/Cell">
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                     <p>Cell Level Modeling</p>
                     </a>
                     </a>
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              </li>
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                    </li>
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          </ul>
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                    <li>
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    </li>
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                    <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Curli/Colony">
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                    <p>Colony Level Modeling</p>
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    <li>
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                    </a>
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                              <li>
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                              <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Curli/Reflection">
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                              <p>Critical reflection on our model</p>
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                              </a>
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                              </li>
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                    </li>
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              </ul>
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           <a href="/Team:TU_Delft-Leiden/Modeling/EET">
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           <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/EET">
           <p>EET Module</p>
           <p>EET Module</p>
           </a>
           </a>
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               <li>
               <li>
                    
                    
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                     <a href="/Team:TU_Delft-Leiden/Modeling/EET/FBA">
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/EET/FBA">
                     <p> Flux Balance Analysis of the EET Module</p>
                     <p> Flux Balance Analysis of the EET Module</p>
                     </a>
                     </a>
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               <li>
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                     <a href="/Team:TU_Delft-Leiden/Modeling/EET/Deterministic">  
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/EET/Deterministic">  
                     <p> Deterministic Model of EET Complex Assembly</p>
                     <p> Deterministic Model of EET Complex Assembly</p>
                     </a>
                     </a>
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         </ul>
         </ul>
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  </li>
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          <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine">
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  <li>
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          <p>Landmine Module</p>
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          </a>
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        <a href="/Team:TU_Delft-Leiden/Modeling/Curli">
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        <p>Curli Module</p>
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          <ul>
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        </a>
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              <ul>
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                    <li>
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                     <a href="/Team:TU_Delft-Leiden/Modeling/Curli#Gene Level">
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              <li>
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                     <p>Gene Level Modeling</p>
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine#simplemodel">
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                     <p>Simple Binding Model </p>
                     </a>
                     </a>
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              </li>
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                    </li>
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              <li>
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine#coopbinding">
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                    <li>
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                     <p>Cooperative Binding Model</p>
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                     <a href="/Team:TU_Delft-Leiden/Modeling/Curli#Cell Level">
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                     <p>Cell Level Modeling</p>
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                     </a>
                     </a>
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              </li>
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    <li>
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                     <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Landmine#experimentaldata">
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                    <li>
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                     <p>Fitting to Experimental Data</p>
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                     <a href="/Team:TU_Delft-Leiden/Modeling/Curli#Colony Level">
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                     <p>Colony Level Modeling</p>
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                     </a>
                     </a>
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               </li>
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                    </li>
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               </ul>
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  </li>
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  <li>
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          </ul>
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          <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/interactions">
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          <p>Interaction with Life Science and Microfluidics</p>
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          </a>
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          <ul>
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              <li>  
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                    <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Life_science/curli/integration">
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                    <p>Curli Module </p>
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                    </a>
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              </li>
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              <li>
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                    <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Life_science/EET/integration">
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                    <p>EET Module </p>
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                    </a>
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              </li>
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                <li>
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                    <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Project/Life_science/landmine/integration">
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                    <p>Landmine Module </p>
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                    </a>
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              </li>
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          </ul>
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           <a href="/Team:TU_Delft-Leiden/Modeling/Techniques">
           <a href="/Team:TU_Delft-Leiden/Modeling/Techniques">
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           </ul>     
           </ul>     
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          <a href="/Team:TU_Delft-Leiden/Modeling/CodeRepository">
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          <p>Code Repository</p>
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          </a>
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    </li>
 
</ul>   
</ul>   
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</div>
</div>
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<h3>Landmine module </h3>
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<h3> References </h3>
<p>
<p>
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An important part of our iGEM project is a promoter sensitive to DNT/TNT. We will use two promoters that are sensitive to DNT/TNT, namely <i>ybiJ</i> and <i>ybiFB2A1</i>, in our project. Of these promoters, not much is known other than the fact that they have a DNT/TNT-dependent response curve . Our goal was to find a model which would be able to reproduce the response curves of both promoters. To achieve this, we constructed two different models, both using <a href="https://2014.igem.org/Team:TU_Delft-Leiden/Modeling/Techniques/Deterministic">Deterministic Modeling Methods</a>. One model is based on a simple binding model of DNT to the promoter, the other is based on cooperative binding of DNT to the promoter.  
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[1] S. Yagur-Kroll, S. Belkin <i>et al.</i>, “<i>Escherichia Coli</i> bioreporters for the detection of 2,4-dinitrotoluene and 2,4,6-trinitrotoluene”, Appl. Microbiol. Biotechnol. 98, 885-895, 2014.  
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When based on the simple binding model, fits of promoter activation with respect to DNT concentration to the experimental data of [1] did not yield good results. However, when the fits were based on the cooperative binding model, we were able to match the experimental data in [1] really well, see figure 1.
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</p>
</p>
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<figure>
 
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<img src="https://static.igem.org/mediawiki/2014/5/59/TUDelft_2014_model_fit_tnt_promoters_coop.png" width="100%" width="100%" height="100%">
 
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<figcaption>
 
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Figure 1: Fits of the promoter activation model described by cooperative promoter activation to the data of [1]. The left panel shows the fit for the jbiJ promoter, the right panel the fit for the yqjFB2A1 promoter. For comparison, also the fits described by the simple binding model are displayed.
 
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</figcaption>
 
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</figure>
 
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<br>
 
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<h3>EET Module </h3>
 
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<h3>References </h3>
 
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<p>
 
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[1] S. Yagur-Kroll, S. Belkin <i>et al.</i>, “<i>Escherichia Coli</i> bioreporters for the detection of 2,4-dinitrotoluene and 2,4,6-trinitrotoluene”, Appl. Microbiol. Biotechnol. 98, 885-895, 2014.
 
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</p>
 
</div>
</div>

Latest revision as of 23:44, 17 October 2014


Modeling Overview

We developed models for each of the three different modules of our project: the conductive curli module, the extracellular electron transport (EET) module and the landmine detection module.
For the conductive curli module, we wanted to know if a conductive path between two electrodes of a chip filled with curli growing E. coli arise at a certain point in time. We also wanted to make quantitative predictions about the resistance between the two electrodes of our system in time.
For the EET module, our goal was to investigate the carbon metabolism providing the electrons for the EET module. Also, we want the EET pathway used by the cells in order to have a measurable electrical signal for our biosensor, see the gadget section of our wiki. Furthermore, in our modeling of the assembly of the EET complex, we wanted to predict how many EET complexes are formed under different initial conditions. We focused, in addition to the assembly mechanism, also on the apparent reduced cell viability.
For the landmine module, we tried to find a model which would be able to reproduce the response curves of both the landmine promoters, as found in [1].
For the EET and landmine modules, we used deterministic modeling. For the curli module, we used a stochastic modeling approach, and considered the system at the gene, cell and colony level. At the colony levvel, we employed percolation theory in order to predict if a conductive path between the two electrodes arise at a certain point in time and to predict at which time this happens. Our application of percolation theory to describe the formation of a conductive biological network represents a novel approach that has not been used in the literature before.


We used Matlab for most of the calculations; the scripts we made can be found in the Code Repository. We had great interactions with the Life Science and Microfluidics departments, which for the conductive curli module can be read here, for the EET module can be read here and for the landmine detection module can be read here.

References

[1] S. Yagur-Kroll, S. Belkin et al., “Escherichia Coli bioreporters for the detection of 2,4-dinitrotoluene and 2,4,6-trinitrotoluene”, Appl. Microbiol. Biotechnol. 98, 885-895, 2014.

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