Team:Evry/Model1

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<h1>Model 1</h1>
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<div id="mainTextcontainer">
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<h1>Duodenum model</h1>
<h2>Overview</h2>
<h2>Overview</h2>
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<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/>
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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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</p>
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<p>This model simulates the behaviour of a hemochromatosis suffering person's duodenum. We compute the quantity of iron absorbed by the organism.
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<a id="Assumptions"></a>
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Our genetically modified bacterias are also released in the duodenum and produce siderophores to chelate the solved iron, thus making it unavailable for intestinal absorption. </p>
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<h2>Assumptions</h2>
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<ul>
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<li>Our bacteria don't settle in the duodenum</li>
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<li>No regulation in the patient's iron absorption</li>
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<li>Constant iron flow</li>
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<li>Homogeneous fluid</li>
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<li>The bacterial quantity is constant</li>
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<li>The bacterial natural absorption is insignificant compared to the chelation</li>
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<li>The patient ingests 20mg of iron per day (Guideline Daily Amounts)</li>
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</ul>
<h2>Model Description </h2>
<h2>Model Description </h2>
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<p>
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<span style="float:right;"> <img src="https://static.igem.org/mediawiki/2013/1/1d/GrapheRaisonnementModele1.png" width=600px /> </span>
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<span style="color:#0000FF;">A</span> : Total quantity of iron absorbed by the duodenum (mol)
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<br/>
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<span style="color:#FF0000;">S</span> : Quantity of solubilized iron (mol)
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<br/>
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P : Total quantity of enterobactin produced by our population of bacteria (mol)
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<br/>
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<span style="color:#00FFFF;">Q</span> : Total quantity of chelated iron (mol)
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<br/>
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N : Number of bacteria
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</p>
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<img src="https://static.igem.org/mediawiki/2013/9/93/EquadiffModele1.png" width=300px /><br/>
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<p>
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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.
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</p>
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Where <img src="https://static.igem.org/mediawiki/2013/0/01/LogistiqueDuodenum.png" /> is our <a href="https://2013.igem.org/Team:Evry/LogisticFunctions">logistic function</a> (which we will here abusively call activator).<br/>
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bla
 
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<h2>Assumptions</h2>
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<a id="Results"></a>
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<h2>Results</h2>
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<p>
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bla
 
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<h2>Equation System</h2>
 
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bla
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<div class="captionedPicture" style="width:100%;">
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  <a title="Absorption" href="https://static.igem.org/mediawiki/2013/4/44/Model_absorption_treatment.png">
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    <img alt="Absorption" src="https://static.igem.org/mediawiki/2013/4/44/Model_absorption_treatment.png" class="Picture"/>
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  </a>
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  <div class="caption">
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    <b>Figure 1 : </b> Iron Absorption in the duodenum with and without treatment.
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  </div>
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</div>
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<br/>
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Figure 1 represent the iron absorbed by the duodenum during a meal. We can see the reduction of iron absorption in the duodenum
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<br/>
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<div class="captionedPicture" style="width:100%;">
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  <a title="Quantity" href="https://static.igem.org/mediawiki/2013/0/07/Model_iron_treatment.png">
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    <img alt="Quantity" src="https://static.igem.org/mediawiki/2013/0/07/Model_iron_treatment.png" class="Picture"/>
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  </a>
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  <div class="caption">
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    <b>Figure 2 : </b> Iron in the duodenum during the simulation
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  </div>
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</div>
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<br/>
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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.
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<h2>Results</h2>
 
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bla
 
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<h2>Conclusion</h2>
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<br/><br/>
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<u>Parameters:</u><br/><br/>
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The simulations was made with following parameters:<br/>
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<table width="100%" border="1">
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<tr width="100%">
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<th>Name</th>
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<th>Value</th>
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<th>Unit</th>
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<th>Description</th>
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<th>Reference</th>
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</tr>
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<tr width="100%">
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<td>alpha</td>
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<td>0.03</td>
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<td>s-1</td>
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<td>Duodenum absorption rate</td>
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<td>-</td>
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</tr>
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<tr width="100%">
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<td>v</td>
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<td>0.007</td>
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<td>m/s</td>
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<td>Chyme's flow average speed</td>
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<td>[1]</td>
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</tr>
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<tr width="100%">
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<td>L</td>
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<td>0.3</td>
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<td>m</td>
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<td>Duodenum length</td>
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<td>[3]</td>
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</tr>
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<tr width="100%">
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<td>delta</td>
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<td>2.65*10^-8</td>
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<td>mol-1</td>
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<td>Dimensional parameter</td>
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<td>-</td>
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</tr>
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<tr width="100%">
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<td>Sp</td>
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<td>4.5*10^-9</td>
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<td>mol/s</td>
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<td>Iron pulse</td>
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<td>[1]</td>
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</tr>
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<tr width="100%">
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<td>K</td>
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<td>100</td>
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<td>mol/s</td>
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<td>Activator Magnitude</td>
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<td>-</td>
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</tr>
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<tr width="100%">
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<td>p</td>
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<td>0.005</td>
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<td>mol/s</td>
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<td>Value at zero of the activator</td>
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<td>-</td>
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</tr>
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<tr width="100%">
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<td>h</td>
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<td>10^-5</td>
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<td>-</td>
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<td>Activator efficiency</td>
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<td>-</td>
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</tr>
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<tr width="100%">
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<td>d</td>
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<td>10^-9</td>
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<td>mol</td>
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<td>Activator threshold</td>
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<td>[2]</td>
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</tr>
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</table>
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bla
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</p><br/>
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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>
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<h2>References</h2>
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<a id="Conclusion"></a>
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<h2>Conclusion</h2>
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bla
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<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.</p>
<div id="citation_box">
<div id="citation_box">
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<p id="references">References:</p>
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<p id="references">References:</p>
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<ol>
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<ol>
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<li><a href="https://2011.igem.org/Team:Imperial_College_London">https://2011.igem.org/Team:Imperial_College_London</a>   </li>
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   <li>Calculated from : Computational Modeling and Simulation of the Human Duodenum - B. Hari, S. Bakalis, P. Fryer - 2012</li>
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<li>Cheng, Y. Dai, C. Zhao, Y. 2006. Auxin biosynthesis by the YUCCA flavin monooxygenases controls the formation of floral organs and vascular tissues in  <i>Arabidopsis</i>. Genes & Dev 20: 1790-1799. Doi: 10.1101/gad.1415106  </li>
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  <li>http://onlinelibrary.wiley.com/doi/10.1016/S0168-6445%2803%2900055-X/pdf p.217 </li>
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<li>Paulsen, M., Legewie, S., Eils, R., Karaulanov, E. & Niehrs, C. 2011. Negative feedback in the bone morphogenetic protein 4 (BMP4) synexpression group governs its dynamic signaling range and canalizes development. PNAS 108, 10202-10207 (Supporting Information Appendixm ,SI Table 1. Kinetic parameters of the model).</li>
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  <li>Wikipedia</li>
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<li>Urakami, M., Ano, R., Kimura, Y., Shima, M., Matsuno, R., Ueno, T. & Akamatsu, M. (2003). Relationship between structure and permeability of tryptophan derivatives across human intestinal epithelial (Caco-2) cells. Zeitschrift für Naturforschung C, Journal of biosciences 58c, 135-42.</li>
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  </ol>
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<li>Brenda: The Comprehensive Enzyme Information System <a href="http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.12.3">http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.12.3</a> </li>
+
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<li><a href="http://biocyc.org/META/NEW-IMAGE?type=ENZYME&object=MONOMER-7661">http://biocyc.org/META/NEW-IMAGE?type=ENZYME&object=MONOMER-7661</a></li>
+
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<li><a href="https://2011.igem.org/Team:Imperial_College_London/Project_Auxin_Modelling">https://2011.igem.org/Team:Imperial_College_London/Project_Auxin_Modelling</a></li>
+
-
  <li>Boado, R. J., Li, J. Y., Nagaya, M., Zhang, C. & Pardridge, W. M. 1999. Selective expression of the large neutral amino acid transporter at the blood–brain barrier. PNAS 96, 12079-12084.</li>
+
-
<li>Kim, D. K., Kanai, Y., Chairoungdua, A., Matsuo, H., Cha, S. H. & Endou, H. 2001. Expression Cloning of a Na+ -independent Aromatic Amino Acid Transporter with Structural Similarity to H+/Monocarboxylate Transporters. J Biol Chem 276, 17221-17228.</li>
+
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<li><a href="http://www.mathworks.fr/fr/help/simbio/ug/example--calculating-sensitivities.html">http://www.mathworks.fr/fr/help/simbio/ug/example--calculating-sensitivities.html</a></li>
+
-
<li>Schillers, H., Danker, T., Schnittler, H.-J., Lang, F. & Oberleithner, H. (2000). Plasma Membrane Plasticity of Xenopus laevis Oocyte Imaged with Atomic Force Microscopy. Cellular Physiol Biochem 10, 1-9.</li>
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</ol>
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</div>
</div>
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<a href="https://static.igem.org/mediawiki/2013/2/2e/Duodenum.zip"> Download the model</a>
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{{:Team:Evry/foot}}

Latest revision as of 09:56, 26 October 2013

Iron coli project

Duodenum model

Overview

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.
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 not give any numerical results.

Assumptions

  • 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)

Model Description

A : Total quantity of iron absorbed by the duodenum (mol)
S : Quantity of solubilized 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.

Figure 1 represent the iron absorbed by the duodenum during a meal. We can see the reduction of iron absorption in the duodenum
Quantity
Figure 2 : Iron in the duodenum during the simulation

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.

Parameters:

The simulations was made with following parameters:
Name Value Unit Description Reference
alpha 0.03 s-1 Duodenum absorption rate -
v 0.007 m/s Chyme's flow average speed [1]
L 0.3 m Duodenum length [3]
delta 2.65*10^-8 mol-1 Dimensional parameter -
Sp 4.5*10^-9 mol/s Iron pulse [1]
K 100 mol/s Activator Magnitude -
p 0.005 mol/s Value at zero of the activator -
h 10^-5 - Activator efficiency -
d 10^-9 mol Activator threshold [2]


There is a slight difference between the two cases, which would possibly allow us to fit the treatment to the patient's characteristics.

Conclusion

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.

References:

  1. Calculated from : Computational Modeling and Simulation of the Human Duodenum - B. Hari, S. Bakalis, P. Fryer - 2012
  2. http://onlinelibrary.wiley.com/doi/10.1016/S0168-6445%2803%2900055-X/pdf p.217
  3. Wikipedia
Download the model

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