Team:Evry/Modeltr2

From 2013.igem.org

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<h2>Observations</h2>
<h2>Observations</h2>
<p>
<p>
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Once our genetically modified bacteria are released in the duodenum, they produce siderophores to chelate the solved iron, thus making it unavailable for intestinal absorption. Then, <b>they eventually flush out of the duodenum</b>. The main hypothesis in this model is that the bacteria don't colonize the duodenum : they only flow through. <br/>
+
Once our genetically modified bacteria are released in the duodenum, they produce siderophores to chelate the solved iron, thus making it unavailable for intestinal absorption. Then, <b>they eventually flush out of the duodenum</b>. The main hypothesis in this model is that the bacteria don't colonize the duodenum : they only flow through. They don't even have time to grow, for the time required to flush through is close to 40s.<br/>
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The goal of this model is to measure how efficient could this form of treatment be. Because too much parameters remain unknown, it is a theoretical simulation which will <b>not</b> give any numerical results.  
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Because some of the parameters remain unknown, it is a theoretical simulation which will <b>not</b> give any numerical results, only qualitative results.
</p>
</p>
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<b><span style="color:#0000FF;">A</span></b> : Total quantity of iron absorbed by the duodenum (mol)
<b><span style="color:#0000FF;">A</span></b> : Total quantity of iron absorbed by the duodenum (mol)
<br/>
<br/>
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<b><span style="color:#FF0000;">S</span></b> : Quantity of solubilized iron (mol)
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<b><span style="color:#FF0000;">S</span></b> : Quantity of solved iron (mol)
<br/>
<br/>
<b>P</b> : Total quantity of enterobactin produced by our population of bacteria (mol)
<b>P</b> : Total quantity of enterobactin produced by our population of bacteria (mol)
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<h2>Results</h2>
<h2>Results</h2>
<p>
<p>
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<a id="Fig1"></a>
<div class="captionedPicture" style="width:100%;">
<div class="captionedPicture" style="width:100%;">
   <a title="Absorption" href="https://static.igem.org/mediawiki/2013/4/44/Model_absorption_treatment.png">
   <a title="Absorption" href="https://static.igem.org/mediawiki/2013/4/44/Model_absorption_treatment.png">
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  </div>
  </div>
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<br/>
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<p>Figure 1 represent the iron absorbed by the duodenum during a meal. We can see the reduction of iron absorption in the duodenum</p>
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<p>The <a href="#Fig1">Figure 1</a> represents the total iron absorbed by the duodenum during an average meal (with and without bacterial treatment), whereas the <a href="#Fig2">Figure 2</a> represents the instant ambient iron (with and without bacterial treatment).
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</p>
<br/>
<br/>
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<a id="Fig2"></a>
  <div class="captionedPicture" style="width:100%;">
  <div class="captionedPicture" style="width:100%;">
   <a title="Quantity" href="https://static.igem.org/mediawiki/2013/0/07/Model_iron_treatment.png">
   <a title="Quantity" href="https://static.igem.org/mediawiki/2013/0/07/Model_iron_treatment.png">
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  </div>
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<p>Figure 2 represent iron disolved in the chyme. This graph point out the influence of bacteria on the middle. The blue curve decrease significantly under the bacteria flux. That underline the fact that the treatment don't affect the absorption directly. After 150 secondes, chyme is no longer in the duodenum, thus the iron absorption is reduce in both cases.<em>Baptiste: En fait je suis pas sûr que ça soit exactement ça, mais faudrait l'expliquer en tout cas même si c'est un artefact.</em></p>
+
<p>
 +
The <a href="#Fig2">Figure 2</a> points out the influence of our bacteria on the middle. The blue curve decreases significantly under the bacterial flow. That underlines the fact that the treatment doesn't directly affect the absorption. After 150 seconds, the chyme is considered to progressively leave the duodenum, thus reducing the iron absorption in both cases, which finally leads to a steady state.
 +
</p>
<br/><br/>
<br/><br/>
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<u>Parameters:</u><br/><br/>
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<h2>Parameters:</h2>
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The simulations was made with following parameters:<br/>
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The simulations was made with following parameters:<br/><br/>
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</p>
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<p>There is a slight difference between the two cases, which would possibly allow us to fit the treatment to the patient's characteristics.</p>
 
<h2>Conclusion</h2>
<h2>Conclusion</h2>
<p>
<p>
-
It is possible to significantly reduce intestinal iron intake if the patient takes one pill before or during each meal. This means that the patient would endure a lighter treatment : less bloodletting for people suffering from hemochromatosis, and less iron chelator's side effects for the thalassemia.
+
The combination of the two curves clearly shows that bacteria would be able to <b>neutralize a significant quantity of iron</b> before it is absorbed by the duodenum.<br/>
 +
It would thus be possible to divide the intestinal iron intake by 2 if the patient takes one pill during each meal. This means that the patient would endure a lighter treatment : less bloodletting for people suffering from hemochromatosis, and less iron chelator's side effects for the thalassemia.
</p>
</p>

Revision as of 14:45, 26 October 2013

Iron coli project

Final flush treatment model

Introduction

This model comes right after the Disease model. We now want to model the flush treatment by simulating a flush of iron-chelating bacteria.

Observations

Once our genetically modified bacteria are released in the duodenum, they produce siderophores to chelate the solved iron, thus making it unavailable for intestinal absorption. Then, they eventually flush out of the duodenum. The main hypothesis in this model is that the bacteria don't colonize the duodenum : they only flow through. They don't even have time to grow, for the time required to flush through is close to 40s.
Because some of the parameters remain unknown, it is a theoretical simulation which will not give any numerical results, only qualitative results.

Goals

This model was made to check if our first strategy was viable. It aims to answer the following question:
"Is it possible to chelate a significant amount of iron with a flush strategy?"

Assumptions

The same assumptions as in the previous model apply:

  • Our bacteria don't settle in the duodenum
  • No regulation in the patient's iron absorption
  • Constant iron flow
  • Homogeneous fluid
  • The bacterial quantity is constant
  • The bacterial natural absorption is insignificant compared to the chelation
  • The patient ingests 20mg of iron per day (Guideline Daily Amounts)

Materials and methods

A : Total quantity of iron absorbed by the duodenum (mol)
S : Quantity of solved iron (mol)
P : Total quantity of enterobactin produced by our population of bacteria (mol)
Q : Total quantity of chelated iron (mol)
N : Number of bacteria


The graph on the right explains the reasoning: for instance, the arrow with a + between N and P means that the variation of P has a positive linear term in N.

Where is our logistic function (which we will here abusively call activator).

Results

Absorption
Figure 1 : Iron Absorption in the duodenum with and without treatment.

The Figure 1 represents the total iron absorbed by the duodenum during an average meal (with and without bacterial treatment), whereas the Figure 2 represents the instant ambient iron (with and without bacterial treatment).


Quantity
Figure 2 : Iron in the duodenum during the simulation. The grey strip represent the presence of the bacteria in the duodenum.

The Figure 2 points out the influence of our bacteria on the middle. The blue curve decreases significantly under the bacterial flow. That underlines the fact that the treatment doesn't directly affect the absorption. After 150 seconds, the chyme is considered to progressively leave the duodenum, thus reducing the iron absorption in both cases, which finally leads to a steady state.



Parameters:

The simulations was made with following parameters:

Name Value Unit Description Reference
Sp 4.5*10^-9 mol.s-1 Iron pulse [1][2]
v 0.007 m.s-1 Chyme's flow average speed [2]
L 0.3 m Duodenum length [3]
α 0.03 s-1 Duodenum absorption rate Disease model
δ 2.65*10^-8 mol-1 Dimensional parameter REF
K 100 mol/s Activator Magnitude set
p 0.005 mol.s-1 Value at zero of the activator set
h 10^-5 - Activator efficiency set
d 10^-9 mol Activator threshold [4]


Conclusion

The combination of the two curves clearly shows that bacteria would be able to neutralize a significant quantity of iron before it is absorbed by the duodenum.
It would thus be possible to divide the intestinal iron intake by 2 if the patient takes one pill during each meal. This means that the patient would endure a lighter treatment : less bloodletting for people suffering from hemochromatosis, and less iron chelator's side effects for the thalassemia.

Models and scripts

References:

  1. Physiol Rev 93: 1721–1741, 2013 doi:10.1152/physrev.00008.2013 - Tomas Ganz "SYSTEMIC IRON HOMEOSTASIS"
  2. Calculated from : Computational Modeling and Simulation of the Human Duodenum - B. Hari, S. Bakalis, P. Fryer - 2012
  3. Wikipedia
  4. Calculated from : http://onlinelibrary.wiley.com/doi/10.1016/S0168-6445%2803%2900055-X/pdf p.217

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