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| !align="center"|[[Team:ULB-Brussels/Parts|Parts]] | | !align="center"|[[Team:ULB-Brussels/Parts|Parts]] |
| !align="center"|[[Team:ULB-Brussels/Modeling|Modeling]] | | !align="center"|[[Team:ULB-Brussels/Modeling|Modeling]] |
| + | !align="center"|[[Team:ULB-Brussels/Conclusion|Conclusion & Perspectives]] |
| !align="center"|[[Team:ULB-Brussels/Safety|Safety]] | | !align="center"|[[Team:ULB-Brussels/Safety|Safety]] |
| !align="center"|[[Team:ULB-Brussels/Previous|Older wiki's]] | | !align="center"|[[Team:ULB-Brussels/Previous|Older wiki's]] |
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| <br></br> | | <br></br> |
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- | <center><font color="#000000"; size="100"> Team ULB-Brussels, modelisation of our </font></center> | + | <center><font color="#000000"; size="100"> Team ULB-Brussels, modeling of our </font></center> |
| <br></br><p><center><font color="#000000"; size="100"> project! </font></center></p> | | <br></br><p><center><font color="#000000"; size="100"> project! </font></center></p> |
| <br></br> | | <br></br> |
- | <table id="toc" class="toc">
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- | <tr>
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- | <td>
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- | <div id="toctitle">
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- | <h2>Sommaire</h2>
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- | </div>
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- | <ul>
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| + | <balise id="hautdepage"></balise> |
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- | <A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#1. Introduction"> 1. Introduction </A>
| + | <p><font size="+3"> An online version of the report can be found <a href="http://www.mediafire.com/view/?ubp5sobban0b9l6">here</a>.</font> |
- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2. Modeling the competition experiment"> 2. Modeling the competition experiment</A> | + | |
- | <ul><p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2.1. Notations and mathematical model"> 2.1. Notations and mathematical model </A>
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- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2.2. Natural selection?"> 2.2. Natural selection? </A></ul>
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- | <ul><p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2.2.1. Neglecting the Microcin diffusion"> 2.2.1. Neglecting the Microcin diffusion </A>
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- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2.2.2. Qualitative discussion of the solutions of (2) in the general case"> 2.2.2. Qualitative discussion of the solutions of (2) in the general case </A>
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- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2.2.3. Conclusion: no natural selection"> 2.2.3. Conclusion: no natural selection </A>
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- | </ul>
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- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#3. New experiment and conclusion"> 3. New experiment and conclusion </A>
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- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#4. Appendix"> 4. Appendix </A>
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- | <ul><p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#4.1. Determining analytically the asymptotical behaviour of the solutions of (1)"> 4.1 Determining analytically the asymptotical behaviour of the solutions of (1) </A>
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- | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#4.2. Parameter estimation"> 4.2. Parameter estimation </A>
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- | </ul>
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- | </td>
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- | </tr>
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- | </table>
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- | | + | |
- | <h2><A NAME="1. Introduction"> 1. Introduction </A></h2>
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- | <p> Since complex biological pathways are used in an industrial way in order to produce molecules of
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- | interest, it has become crucial to understand and, above all, optimize these pathways. However,
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- | biological systems are so complex that it is sometimes impossible to have a complete understanding
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- | of the reactions and mechanisms of the di�erent pathways. The idea of our project is to solve this
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- | optimization problem by using the integron platform { which represents a natural genetic optimiza-
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- | tion tool in bacteria { and putting in competition di�erent populations with di�erent gene orders,
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- | so that the population(s) with the optimal order(s) will be naturally selected with time.
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- | <p> As a proof of concept, we will try to optimize the order of the genes governing the production of
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- | two natural antibiotics: Microcin C7 and Microcin B17. The �rst one inhibits a tRNA synthetase
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- | (thus inhibits protein synthesis and, as a consequence, cell division), and the second inhibits a gyrase
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- | (thus provokes inhibition of DNA replication and eventually cell death). We might then expect that
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- | natural selection occurs, so that the optimal gene order(s) �nally emerge.
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- | <p> In the sequel, we model this competition experiment, and try to see in what sense and in what
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- | conditions natural selection could happen.
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- | <td><a href=""#hautdepage""><img id="logo" src="http://www.clker.com/cliparts/9/2/8/c/1216180855712705788claudita_home_icon.svg.hi.png" height="40px" width="40px" align="right"></a>
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| <br></br> | | <br></br> |
- | | + | <embed src="http://data.axmag.com/data/201209/U59129_F130176/main.swf?page=81" quality="high" width="100%" height="650px"; scale="noscale" align="TL" salign="TL" allowFullScreen="true" type="application/x-shockwave-flash"></embed> |
- | <h2><A NAME="2. Modeling the competition experiment"> 2. Modeling the competition experiment</A></h2> | + | |
- | <p> In the following, we write Microcins <em>B</em> and <em>C</em> for Microcins <em>B17</em> and <em>C7</em>, respectively. Further,
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- | the bacterial populations producing these antibiotics will be denoted by <em>Bi</em> and <em>Cj</em> , respectively,
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- | where the indices i and j run through all di�erent gene cassette orders.
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- | <p> We consider the experiment where all these populations are put in competition together. In our
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- | model, for the sake of simplicity, we will simply consider that Microcin <em>B</em> causes the production of
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- | some protein complexes that provoke cell death (bactericidal), while Microcin <em>C</em> inhibits cell division
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- | of the protein complexes that allow the cellular division process. (bacteriostatic). Thus note that the quantities <em>AXi</em> and <em>DXi</em> have no biological meaning, but are
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- | used phenomenologically to better describe the situation.
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| <br></br> | | <br></br> |
- | <h3><A NAME="2.1. Notations and mathematical model"> 2.1. Notations and mathematical model</A></h3> | + | <center> |
- | <p> The study of the di�erent populations will be accomplished through the time evolution of the following dynamical quantities. Notice that subscribed letters will designate the given population, while
| + | Here are the several graphs that did not appear on the reading version above. |
- | superscripted letters will stand for the corresponding antibiotics.
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- | | + | |
- | <img id="logo" src="https://static.igem.org/mediawiki/2012/a/aa/Model_1.PNG" height="65%" width="65%">
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- | | + | |
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- | <p> Using these constants and dynamical variables, we can describe the biological competition experiment by the following di�erential equation system (where <em>X = B;C</em> and i runs through all the
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- | di�erent possible gene orders for the antibiotics production gene cassettes):
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- | <img id="logo" src="https://static.igem.org/mediawiki/2012/5/55/Model_2.PNG" height="65%" width="65%">
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- | | + | |
- | <p> This general model can be simpli�ed if we suppose that populations <em>Xi</em> are completely immune to Microcin <em>X</em>, which is a totally reasonable assumption. Further, since bacteria and Microcins have
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- | half-lives that are much larger than the experiment time, we may neglect the corresponding terms.
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- | If we also neglect the saturation e�ect in the population growth (which is natural if the experiment
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- | is carried out in exponential phase), we then get the following simpler system:
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- | <img id="logo" src="https://static.igem.org/mediawiki/2012/6/6f/Model_3.PNG" height="65%" width="65%">
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| <br></br> | | <br></br> |
- | | + | <img id="logo" src="https://static.igem.org/mediawiki/2012/6/6a/Graphe_1.PNG" > |
- | <h3><A NAME="2.2. Natural selection?"> 2.2. Natural selection?</A></h3> | + | <img id="logo" src="https://static.igem.org/mediawiki/2012/3/3f/Graphe_2.PNG" > |
- | <p> We could hope that putting together bacteria with all the di�erent gene orders leads to a natural | + | |
- | selection regime, meaning that the subpopulations with the best o�ensive and/or defensive charac-
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- | teristics
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| <br></br> | | <br></br> |
- | <h2><A NAME="4. Appendix"> 4. Appendix</A></h2> | + | <font size="+0"> Figures 1-8</font> |
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| <br></br> | | <br></br> |
- | | + | <img id="logo" src="https://static.igem.org/mediawiki/2012/2/2e/Graphe_3.PNG" > |
- | <h3><A NAME="4.1. Determining analytically the asymptotical behaviour of the solutions of (1)"> 4.1. Determining analytically the asymptotical behaviour of the solutions of (1)</A></h3> | + | |
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| <br></br> | | <br></br> |
- | | + | <font size="+0"> Figure 9</font> |
- | <h3><A NAME="4.2. Parameter estimation"> 4.2. Parameter estimation</A></h3> | + | |
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| + | <br></br> |
| + | <td><a href=""#hautdepage""><img id="logo" src="http://www.clker.com/cliparts/9/2/8/c/1216180855712705788claudita_home_icon.svg.hi.png" height="40px" width="40px" align="right"></a> |
| <br></br> | | <br></br> |
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| <h2></h2> | | <h2></h2> |
- | | + | </center> |
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| <br></br> | | <br></br> |