|
|
| (24 intermediate revisions not shown) |
| Line 1: |
Line 1: |
| | <html xmlns="http://www.w3.org/1999/xhtml" lang="en"> | | <html xmlns="http://www.w3.org/1999/xhtml" lang="en"> |
| | + | |
| | | | |
| | <img id="logo" src="https://static.igem.org/mediawiki/2012/8/87/Bac.jpg" height="25%" width="25%"> | | <img id="logo" src="https://static.igem.org/mediawiki/2012/8/87/Bac.jpg" height="25%" width="25%"> |
| Line 14: |
Line 15: |
| | !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]] |
| Line 25: |
Line 27: |
| | <br></br> | | <br></br> |
| | | | |
| - | <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">
| |
| - | <tr>
| |
| - | <td>
| |
| - | <div id="toctitle">
| |
| - | <h2>Sommaire</h2>
| |
| - | </div>
| |
| - | <ul>
| |
| | | | |
| | | | |
| | + | <balise id="hautdepage"></balise> |
| | | | |
| - | <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>
| + | |
| - | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#2.2. Natural selection?"> 2.2. Natural selection? </A></ul>
| + | |
| - | <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>
| + | |
| - | <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>
| + | |
| - | <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>
| + | |
| - | </ul>
| + | |
| - | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#3. New experiment and conclusion"> 3. New experiment and conclusion </A>
| + | |
| - | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#4. Appendix"> 4. Appendix </A>
| + | |
| - | <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>
| + | |
| - | <p><A HREF="https://2012.igem.org/Team:ULB-Brussels/Team#4.2. Parameter estimation"> 4.2. Parameter estimation </A>
| + | |
| - | </ul>
| + | |
| - | </td>
| + | |
| - | </tr>
| + | |
| - | </table>
| + | |
| - | | + | |
| - | <h2><A NAME="1. Introduction"> 1. Introduction </A></h2>
| + | |
| - | <p> <math>\mu</math>Since complex biological pathways are used in an industrial way in order to produce molecules of
| + | |
| - | interest, it has become crucial to understand and, above all, optimize these pathways. However,
| + | |
| - | biological systems are so complex that it is sometimes impossible to have a complete understanding
| + | |
| - | of the reactions and mechanisms of the different pathways. The idea of our project is to solve this
| + | |
| - | optimization problem by using the integron platform { which represents a natural genetic optimiza-
| + | |
| - | tion tool in bacteria { and putting in competition different populations with different gene orders,
| + | |
| - | so that the population(s) with the optimal order(s) will be naturally selected with time.
| + | |
| - | <p> As a proof of concept, we will try to optimize the order of the genes governing the production of
| + | |
| - | two natural antibiotics: Microcin C7 and Microcin B17. The first one inhibits a tRNA synthetase
| + | |
| - | (thus inhibits protein synthesis and, as a consequence, cell division), and the second inhibits a gyrase
| + | |
| - | (thus provokes inhibition of DNA replication and eventually cell death). We might then expect that
| + | |
| - | natural selection occurs, so that the optimal gene order(s) finally emerge.
| + | |
| - | <p> In the sequel, we model this competition experiment, and try to see in what sense and in what
| + | |
| - | conditions natural selection could happen.
| + | |
| - | <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> |
| - | | + | <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,
| + | |
| - | the bacterial populations producing these antibiotics will be denoted by <em>Bi</em> and <em>Cj</em> , respectively,
| + | |
| - | where the indices i and j run through all different gene cassette orders.
| + | |
| - | <p> We consider the experiment where all these populations are put in competition together. In our
| + | |
| - | model, for the sake of simplicity, we will simply consider that Microcin <em>B</em> causes the production of
| + | |
| - | some protein complexes that provoke cell death (bactericidal), while Microcin <em>C</em> inhibits cell division
| + | |
| - | 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
| + | |
| - | used phenomenologically to better describe the situation.
| + | |
| | <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 different 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.
| + | |
| - | | + | |
| - | <img id="logo" src="https://static.igem.org/mediawiki/2012/a/aa/Model_1.PNG" height="65%" width="65%">
| + | |
| - | | + | |
| - | | + | |
| - | <p> Using these constants and dynamical variables, we can describe the biological competition experiment by the following differential equation system (where <em>X = B;C</em> and i runs through all the
| + | |
| - | different possible gene orders for the antibiotics production gene cassettes):
| + | |
| - | <img id="logo" src="https://static.igem.org/mediawiki/2012/5/55/Model_2.PNG" height="65%" width="65%">
| + | |
| - | | + | |
| - | <p> This general model can be simplified 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
| + | |
| - | half-lives that are much larger than the experiment time, we may neglect the corresponding terms.
| + | |
| - | If we also neglect the saturation effect in the population growth (which is natural if the experiment
| + | |
| - | is carried out in exponential phase), we then get the following simpler system:
| + | |
| - | <img id="logo" src="https://static.igem.org/mediawiki/2012/6/6f/Model_3.PNG" height="65%" width="65%">
| + | |
| - | | + | |
| | <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 different gene orders leads to a natural
| + | |
| - | selection regime, meaning that the subpopulations with the best offensive and/or defensive charac-
| + | |
| - | teristics ( ) will be those
| + | |
| - | with the best chances of reproduction, thus leading to the emergence of the bacteria with an optimal
| + | |
| - | gene order.
| + | |
| - | <p> However, we will see in this section that natural selection can only happen on the basis of the
| + | |
| - | immunity properties of the di�erent subpopulations, so that, within subpopulations <em>Bi</em> (resp. <em>Ci</em>),
| + | |
| - | the most immune ones will emerge, - which is unfortunately not interesting for us as we initially
| + | |
| - | aimed to select the most productive ones. We �rst rigorously prove this fact in a simpli�ed context,
| + | |
| - | and then discuss numerical simulations of our model in the general case.
| + | |
| | <br></br> | | <br></br> |
| - | | + | <font size="+0"> Figures 1-8</font> |
| - | <A NAME="2.2.1. Neglecting the Microcin diffusion"> 2.2.1. Neglecting the Microcin diffusion</A> | + | |
| - | <p> In this paragraph, we neglect the di�usion e�ects of the Microcins: in other words, we stop distinguishing between Microcins inside and outside bacteria.
| + | |
| - | | + | |
| - | <A NAME="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>
| + | |
| - | <p> We now discuss the impact of di�erent production and immunity rates on the time evolution of
| + | |
| - | the solutions of general system (2). Since �nding solutions analytically seems beyond possibilities,
| + | |
| - | we use <em>Mathematica 8</em> to solve the system numerically (with biologically reasonable values of the
| + | |
| - | parameters) in the special case when there are only two di�erent gene orders per type (<em>Bi</em>, <em>Ci</em>,
| + | |
| - | i = 1; 2): see Figures 1-8 for a few numerical simulations of the relationship between populations <em>B1</em>,
| + | |
| - | <em>B2</em> (blue and red), as well as <em>C1</em> and <em>C2</em> (green and yellow). All populations have the same initial
| + | |
| - | value.
| + | |
| - | <p>  In Figures 1-7, both populations B (resp. C) have the same immunity but di�erent production rates � . We immediately observe that both populations B (resp. C) have exactly the same behaviour,
| + | |
| - | so that absolutely no di�erence can be seen on the �gures (on each graph, only two double curves
| + | |
| - | can be seen: red/blue for the two populations B and green/yellow for the two populations C).
| + | |
| - | More precisely, numerical simulations show that both populations B (resp. C) behave as one single
| + | |
| - | population with production rate
| + | |
| - | <h2><A NAME="4. Appendix"> 4. Appendix</A></h2>
| + | |
| - | | + | |
| - | | + | |
| | <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> | + | |
| - | | + | |
| - | | + | |
| | <br></br> | | <br></br> |
| - | | + | <font size="+0"> Figure 9</font> |
| - | <h3><A NAME="4.2. Parameter estimation"> 4.2. Parameter estimation</A></h3> | + | |
| | | | |
| | | | |
| | + | <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> |
| | | | |
| | <h2></h2> | | <h2></h2> |
| - | | + | </center> |
| | | | |
| | <br></br> | | <br></br> |
"
