Team:Evry/flush model

From 2013.igem.org

(Difference between revisions)
 
(30 intermediate revisions not shown)
Line 6: Line 6:
<h1>Flush model overview</h1>
<h1>Flush model overview</h1>
 +
<h2>Introduction</h2>
 +
<img src="https://static.igem.org/mediawiki/2013/9/91/Tube_digestif2.jpg" alt="Intestine" width="20%" style="float:right;"/>
<p>
<p>
-
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.
+
In the very beginning of the project, we focused on iron absorption by the duodenum. We first had to model the behaviour of the duodenum regarding iron absorption to determine if a flush treatment strategy was viable. Then we wanted to model the flush treatment by simulating a flush of iron-chelating bacteria.
-
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.  
+
</p>
 +
<br/>
 +
<h2>Disease model</h2>
 +
<p>
 +
We first modeled the iron absorption of a hemochromatosic patient using ODEs.
 +
</p>
 +
<p>
 +
<a href="https://2013.igem.org/Team:Evry/Modeltr1">Here is the link to the disease model</a>.
</p>
</p>
-
<table width="100%">
+
<h2>Treatment model</h2>
 +
<p>
 +
We then used the disease model as a base to develop our flush treatment model. It aims to answer the following question:<br/>
 +
<em>"Is it possible to chelate a significant amount of iron with a flush strategy?"</em>
 +
</p>
 +
<p>
 +
<a href="https://2013.igem.org/Team:Evry/Modeltr2">Here is the link to the treatment model</a>.
 +
</p>
 +
 
 +
 
 +
<br/><br/><br/><br/><br/><br/>
 +
<!--
 +
<h2>Observations</h2>
 +
 
 +
<p>
 +
We know that 60% of iron is absorbed in the duodenum and 40% in the jejunum. The duodenum is located in the upper intestines, right after the stomach, and is usually 300mm long.
 +
<br/>
 +
A healthy person absorbs about 10% (2mg a day) of the daily iron uptake, while a hemochromatosic patient's absorption varies between 50% and 100% of the daily iron uptake.
 +
<div align="center">
 +
<a id="Fig1"></a>
 +
<div class="captionedPicture" style="width:50%;">
 +
  <a title="Absorption" href="https://static.igem.org/mediawiki/2013/3/37/Regulation.png">
 +
    <img alt="Absorption" src="https://static.igem.org/mediawiki/2013/3/37/Regulation.png" class="Picture"/>
 +
  </a>
 +
  <div class="caption">
 +
    <b>Figure 1 : </b> Overview of the iron regulation system in human body.
 +
  </div>
 +
</div>
 +
</div>
 +
<p>
 +
Iron absorption is normally regulated by the liver through hepcidin production (depicted in <a href="#Fig1">Figure 1</a>). This means that after a certain delay, iron absorption eventually reaches a stationary phase.
 +
 
 +
 
 +
Once our genetically modified bacteria are released in the duodenum lumen, 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 do not colonize the duodenum : they only flow through. They do not even have time to grow, for the time required to flush through is close to 40 seconds.<br/>
 +
 
 +
</p>
 +
 
 +
<h2>Goals</h2>
 +
<p>
 +
We wanted to build a generic duodenal iron absorption model so that:
 +
<ul>
 +
<li>We can have a realistic model of iron absorption: <em>"How iron is absorbed in an healthy person and in a sick patient ? </em></li>
 +
<li>We can know how our first strategy of treatment would work: <em>"Is it possible to chelate a significant amount of iron with a flush strategy?"</em></li>
 +
 
 +
 
 +
</ul>
 +
</p>
 +
 
 +
<h2>Materials and Methods</h2>
 +
 
 +
 
 +
 
 +
 
 +
<h3>Assumptions</h3>
 +
<p>With use this same assumptions in our model:
 +
<ul>
 +
<li>Our bacteria don't settle in the duodenum</li>
 +
<li>No regulation in the patient's iron absorption</li>
 +
<li>Constant iron flow in the duodenum lumen</li>
 +
<li>Homogeneous fluid</li>
 +
<li>The bacterial quantity is constant</li>
 +
<li>The bacterial natural absorption is insignificant compared to the chelation</li>
 +
<li>The patient ingests 20mg of iron per day (Guideline Daily Amounts)</li>
 +
</ul>
 +
<h3>Model</h3>
 +
 
 +
<p>We use Ordinary Differential Equation to modelize the duodenum and the potentiel impact of our flush strategy treatment:
 +
<p>
 +
<span style="float:right;"> <img src="https://static.igem.org/mediawiki/2013/1/1d/GrapheRaisonnementModele1.png" style="width:60%;" /> </span>
 +
<b><span style="color:#0000FF;">A</span></b> : Total quantity of iron absorbed by the duodenum (mol)
 +
<br/>
 +
<b><span style="color:#FF0000;">S</span></b> : Quantity of solved iron in the duodenum lumen (mol)
 +
<br/>
 +
<b>P</b> : Total quantity of enterobactin produced by our population of bacteria (mol)
 +
<br/>
 +
<b><span style="color:#00FFFF;">Q</span></b> : Total quantity of chelated iron (mol)
 +
<br/>
 +
<b>N</b> : Number of bacteria
 +
</p>
 +
<img src="https://static.igem.org/mediawiki/2013/1/1b/Duoeqcoul.png" style="width:25%;" /><br/>
 +
<p>
 +
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.
 +
<br/>
 +
<table border="1" style="border-collapse:collapse;">
<tr>
<tr>
-
<td align="center">img1</td>
+
<td><b>S<sub>p</sub></b></td>
-
<td align="center">img2</td>
+
<td>mol.s<sup>-1</sup></td>
-
<td align="center">img3</td>
+
<td>Iron pulse</td>
</tr>
</tr>
<tr>
<tr>
-
<td align="center">txt1</td>
+
<td><b>v</b></td>
-
<td align="center"></td>
+
<td>m.s<sup>-1</sup></td>
-
<td align="center">txt3</td>
+
<td>Chyme's flow average speed</td>
 +
</tr>
 +
<tr>
 +
<td><b>L</b></td>
 +
<td>m</td>
 +
<td>Duodenum length</td>
 +
</tr>
 +
<tr>
 +
<td><b>α</b></td>
 +
<td>s<sup>-1</sup></td>
 +
<td>Duodenum absorption rate</td>
 +
</tr>
 +
<tr>
 +
<td><b>K</b></td>
 +
<td>mol/s</td>
 +
<td>Activator Magnitude</td>
 +
</tr>
 +
<tr>
 +
<td><b>p</b></td>
 +
<td>mol.s<sup>-1</sup></td>
 +
<td>Value at zero of the activator</td>
 +
</tr>
 +
<tr>
 +
<td><b>h</b></td>
 +
<td>-</td>
 +
<td>Activator efficiency</td>
 +
</tr>
 +
<tr>
 +
<td><b>d</b></td>
 +
<td>mol</td>
 +
<td>Activator threshold</td>
 +
</tr>
 +
<tr>
 +
<td><b>δ</b></td>
 +
<td>mol<sup>-1</sup></td>
 +
<td>Dimensional parameter</td>
</tr>
</tr>
</table>
</table>
 +
<br/><br/>
 +
 +
</p>
 +
 +
 +
 +
 +
<h2>Results</h2>
 +
<p>With our ODE system, we were able to answer to the questions presented at the begining of the page. The results are presented on the two following pages:
 +
</p>
 +
<ol>
 +
<li>Disease model on <a href="https://2013.igem.org/Team:Evry/Modeltr1">this</a> page.</li>
 +
<li>The potential effects of our treatment on <a href="https://2013.igem.org/Team:Evry/Modeltr2">this</a> page.</li>
 +
</ol>
 +
 +
 +
 +
 +
<h2>Conclusion</h2>
 +
<p>Our model show that our <b><span style="color:#bb8900">Iron</span><span style="color:#7B0000"> Coli</span></b> with a flush strategy would be able to neutralize a significant quantity of iron before it is absorbed by the duodenum.
 +
It would thus be possible to approximately 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>
 +
 +
<h2>Models and scripts</h2>
 +
<p>
 +
This model was made using the Python language. You can download the python script <a href="https://static.igem.org/mediawiki/2013/2/2e/Duodenum.zip"> here</a>.
 +
</p>
 +
 +
<a id="Ref"></a>
 +
<div id="citation_box">
 +
<p id="references"><b>References:</b></p>
 +
<ul>
 +
<li>Physiol Rev 93: 1721–1741, 2013 doi:10.1152/physrev.00008.2013 - Tomas Ganz "SYSTEMIC IRON HOMEOSTASIS"</li>
 +
  <li>Calculated from : Computational Modeling and Simulation of the Human Duodenum - B. Hari, S. Bakalis, P. Fryer - 2012</li>
 +
  <li>Calculated from : Bacterial iron homeostasis - Simon C. Andrews, Andrea K. Robinson, Francisco Rodriguez-Quinones</li>
 +
  <li>Wikipedia</li>
 +
</ul>
 +
</div>
 +
-->
</html>
</html>
{{:Team:Evry/foot}}
{{:Team:Evry/foot}}

Latest revision as of 02:58, 29 October 2013

Iron coli project

Flush model overview

Introduction

Intestine

In the very beginning of the project, we focused on iron absorption by the duodenum. We first had to model the behaviour of the duodenum regarding iron absorption to determine if a flush treatment strategy was viable. Then we wanted to model the flush treatment by simulating a flush of iron-chelating bacteria.


Disease model

We first modeled the iron absorption of a hemochromatosic patient using ODEs.

Here is the link to the disease model.

Treatment model

We then used the disease model as a base to develop our flush treatment model. It aims to answer the following question:
"Is it possible to chelate a significant amount of iron with a flush strategy?"

Here is the link to the treatment model.







Retrieved from "http://2013.igem.org/Team:Evry/flush_model"