Difference between revisions of "Team:ETH Zurich/Model/In Silico Final"

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     <section class="first">
 
     <section class="first">
 
         <!--<h1>What</h1>-->
 
         <!--<h1>What</h1>-->
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         <p><em>All our experimental and modeling efforts converge here.</em></p>
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         <p><em>All our efforts converge here.</em></p>
 
     </section>
 
     </section>
  
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     <!--<section>
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     <section>
 
         <h1>Final Conclusion</h1>
 
         <h1>Final Conclusion</h1>
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         <p class="description"></p>
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         <p class="description">We <a href="https://2017.igem.org/Team:ETH_Zurich/Model/Environment_Sensing/parameter_fitting">fitted</a> our parameters using experimental data and tuned our own <a href="https://2017.igem.org/Team:ETH_Zurich/Model/Environment_Sensing/AND_gate_fitting">hybrid promoter</a> and integrated it into our 3D model to verify the behavior of our circuit in real-life conditions of tumor colonization.</p>.
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     </section>
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        <h2></h2>
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        <p class="description"> </p>
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     </section>-->
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     <section>
 
     <section>
 
         <h1>Results</h1>
 
         <h1>Results</h1>
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         <p class="description">After fitting the model describing the behavior of our circuit on our experimental data, we simulated the response of our whole circuit including both versions A and B of our <a href="https://2017.igem.org/Team:ETH_Zurich/Model/Environment_Sensing/AND_gate_fitting#sec1">hybrid promoter</a> to test their impact on our sensing circuit in the real-life scenario of tumor colonization and asses their performance.</p>
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         <p class="description">We simulated both our <a href="https://2017.igem.org/Team:ETH_Zurich/Model/Environment_Sensing/AND_gate_fitting#sec1">hybrid promoters</a> <strong>A</strong> and <strong>B</strong> to test the functioning of our sensing circuit in the real-life scenaario of tumor colonization and all different cases of <em>d</em><sub>cell</sub> and Lactate. </p>
  
 
         <figure class="fig-float" style="max-width: 600px;">
 
         <figure class="fig-float" style="max-width: 600px;">
 
             <img src="https://static.igem.org/mediawiki/2017/d/d0/T--ETH_Zurich--Azu_Prom_A.gif"
 
             <img src="https://static.igem.org/mediawiki/2017/d/d0/T--ETH_Zurich--Azu_Prom_A.gif"
 
                 alt="Azu_PromoterA_Gif" />
 
                 alt="Azu_PromoterA_Gif" />
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             <figcaption>Figure 1: Simulation showing our Hybrid promoter version A turning ON in case of Tumor colonization</figcaption>
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             <figcaption>Figure 1: Simulation showing our Hybrid promoter <strong>Version A</strong> turning ON in case of Tumor colonization.</figcaption>
 
         </figure>
 
         </figure>
 
         <figure class="fig-float" style="max-width: 600px;">
 
         <figure class="fig-float" style="max-width: 600px;">
 
             <img src="https://static.igem.org/mediawiki/2017/7/77/T--ETH_Zurich--Azu_Prom_B.gif"
 
             <img src="https://static.igem.org/mediawiki/2017/7/77/T--ETH_Zurich--Azu_Prom_B.gif"
 
                 alt="Azu_PromoterB_Gif" />
 
                 alt="Azu_PromoterB_Gif" />
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             <figcaption>Figure 2: Simulation showing our Hybrid promoter version B turning ON in case of Tumor colonization</figcaption>
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             <figcaption>Figure 2: Simulation showing our Hybrid promoter <strong>Version B</strong> turning ON in case of Tumor colonization.</figcaption>
 
         </figure>
 
         </figure>
  
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             <img src="https://static.igem.org/mediawiki/2017/3/3c/T--ETH_Zurich--Azu_PromoterA.png"
 
             <img src="https://static.igem.org/mediawiki/2017/3/3c/T--ETH_Zurich--Azu_PromoterA.png"
 
                 alt="Azu_PromoterA" />
 
                 alt="Azu_PromoterA" />
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             <figcaption>Figure 1: Azurin concentration for the case of our hybrid promoter version A.</figcaption>
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             <figcaption>Figure 3: Azurin concentration for the case of our hybrid promoter <strong>Version A</strong>.</figcaption>
 
         </figure>
 
         </figure>
 
         <figure class="fig-float" style="max-width: 600px;">
 
         <figure class="fig-float" style="max-width: 600px;">
 
             <img src="https://static.igem.org/mediawiki/2017/2/26/T--ETH_Zurich--Azu_PromoterB.png"
 
             <img src="https://static.igem.org/mediawiki/2017/2/26/T--ETH_Zurich--Azu_PromoterB.png"
 
                 alt="Azu_PromoterB" />
 
                 alt="Azu_PromoterB" />
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             <figcaption>Figure 2: Azurin concentration for the case of our hybrid promoter version B.</figcaption>
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             <figcaption>Figure 4: Azurin concentration for the case of our hybrid promoter <strong>Version B</strong>.</figcaption>
 
         </figure>
 
         </figure>
  
 
         <h2>Inference</h2>
 
         <h2>Inference</h2>
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         <p class="description"> Figures 1 and 2, show that both our promoters fully turn ON in case of High <em>d</em><sub>cell</sub> and High [Lac]. From Figures 3 and 4, a substantial differentiation can be made between both hybrid promoters A and B.</p>
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         <p class="description"> Figures 1 and 2, show that both our promoters are <span style="color:green">FULLY ON</span> in case of High <em>d</em><sub>cell</sub> and High [Lac] conditions of tumor colonization - there is a difference in the time of start of switch ON between the promoters; promoter A switches ON earlier. From Figures 3 and 4, a comparison can be made between the Hybrid promoters A and B. The Promoter B helps achieves a higher steady state Azurin concentration but is less specific as compared to promoter A, as is clearly shown by the difference in steady state concentrations between the High <em>d</em><sub>cell</sub>, High [Lac] and High <em>d</em><sub>cell</sub>, Low [Lac] conditions for each promoter.</p>
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<p>The promoter B helps achieves a higher steady state of azurin concentration but is less specific as compared to promoter A, which exhibits a significantly higher fold-change from the low lactate, high cell density situation.</p>
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    </section>
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</section>
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<section class="emphasize">
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    <section class="emphasize">
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<h1 id="concl">Conclusion</h1>
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        <h1 id="concl">Conclusion</h1>
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<p>By choosing one promoter or the other, our bacterial system can adapt to the specific needs of the clinical application. <strong>For our case, as azurin as been shown to be rather specific towards tumor cells, we would want to go for the promoter B.</strong> However, if we were to implement a more potent and less target cytotoxic agent, <a href="https://2017.igem.org/Team:ETH_Zurich/Model/In_Vivo#InVivo_Killing">as previously suggested</a>, we would definitely choose the promoter A.</p>
+
        <p>By choosing one promoter or the other, our bacterial system can adapt to the specific needs of the clinical application. <strong>For our case, as azurin as been shown to be rather specific towards tumor cells, we would want to go for the promoter B.</strong> However, if we were to implement a more potent and less target cytotoxic agent, <a href="https://2017.igem.org/Team:ETH_Zurich/Model/In_Vivo#InVivo_Killing">as previously suggested</a>, we would definitely choose the promoter A.</p>
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</section>
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    </section>
  
 
</main>
 
</main>
 
</html>
 
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{{ETH_Zurich/Footer_N}}
 
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Revision as of 00:39, 2 November 2017

Simulated Behavior of Our Whole System In-Vivo

All our efforts converge here.

Final Conclusion

We fitted our parameters using experimental data and tuned our own hybrid promoter and integrated it into our 3D model to verify the behavior of our circuit in real-life conditions of tumor colonization.

.

Results

We simulated both our hybrid promoters A and B to test the functioning of our sensing circuit in the real-life scenaario of tumor colonization and all different cases of dcell and Lactate.

Azu_PromoterA_Gif
Figure 1: Simulation showing our Hybrid promoter Version A turning ON in case of Tumor colonization.
Azu_PromoterB_Gif
Figure 2: Simulation showing our Hybrid promoter Version B turning ON in case of Tumor colonization.
Azu_PromoterA
Figure 3: Azurin concentration for the case of our hybrid promoter Version A.
Azu_PromoterB
Figure 4: Azurin concentration for the case of our hybrid promoter Version B.

Inference

Figures 1 and 2, show that both our promoters are FULLY ON in case of High dcell and High [Lac] conditions of tumor colonization - there is a difference in the time of start of switch ON between the promoters; promoter A switches ON earlier. From Figures 3 and 4, a comparison can be made between the Hybrid promoters A and B. The Promoter B helps achieves a higher steady state Azurin concentration but is less specific as compared to promoter A, as is clearly shown by the difference in steady state concentrations between the High dcell, High [Lac] and High dcell, Low [Lac] conditions for each promoter.

Conclusion

By choosing one promoter or the other, our bacterial system can adapt to the specific needs of the clinical application. For our case, as azurin as been shown to be rather specific towards tumor cells, we would want to go for the promoter B. However, if we were to implement a more potent and less target cytotoxic agent, as previously suggested, we would definitely choose the promoter A.