|
|
| Line 1: |
Line 1: |
| - | {{:Team:Freiburg_Bioware/Head}}
| |
| - | {{:Team:Freiburg_Bioware/menu_modeling}}
| |
| | | | |
| - | <html>
| |
| - |
| |
| - |
| |
| - | <h1>Modeling</h1>
| |
| - | For the modeling part we considered three main parts:
| |
| - | <ul>
| |
| - | <li>the virus production
| |
| - | <li>the infection of a target cell
| |
| - | <li>the therapy
| |
| - | </ul>
| |
| - | For the first two models we assumed reactions according to the law of mass action to create a model of ordinary differential equations (ODE).
| |
| - | <br><br>
| |
| - | <h2>Model for Virus Production</h2>
| |
| - | <br>
| |
| - | <h3>Reaction Scheme</h3>
| |
| - | Reducing the complexity of virus production we divide the cell into three compartments: the <b>extracellular matrix</b> (all quantities with the index <i>ext</i>), the <b>cytoplasm</b> (<i>cyt</i>) and the <b>nucleus</b> (<i>nuc</i>). Four plasmids are transfected - the plasmid coding for the <b>helper proteins</b> (<i>helper</i>), the <b>gene of interest</b> (<i>goi</i>) and two types of plasmids coding for the <b>capsid proteins</b> (<i>capwt</i> [wild type], <i>capmod</i> [modified]).<br>
| |
| - | The plasmids are transported into the nucleus where gene expression is initiated. Processed mRNA is transported into the cytoplasm and <b>proteins</b> (<i>phelper</i>, <i>pcapwt</i>, <i>pcapmod</i>) are produced. Containing a nuclear localization sequence proteins are relocated into the nucleus where capsid assembly occurs. The viral capsid is compose of 60 subunits of viral coat proteins. Titration of the two plasmids coding for the capsid proteins leads to virus surfaces with different ratios of wild type and modified capsid proteins.<br>
| |
| - | The gene of interest is replicated by cellular polymerases and <b>single stranded DNA</b> (<i>ssDNA</i>) is encapsidated into the preformed <b>capsids</b> (<i>capsid</i>) forming infectious <b>viral particles</b> (<i>V</i>).<br>
| |
| - | Finally the recombinant viruses are released into the extracellular matrix and can be harvested for transduction.
| |
| - |
| |
| - | <br><br>
| |
| - |
| |
| - | <center>
| |
| - | <img width="733" height="966" src="https://static.igem.org/mediawiki/2010/b/b8/Freiburg10_VirusProduction01.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - | <br><br>
| |
| - | <h3>Reduced Reaction Scheme</h3>
| |
| - | Even the coarse model for virus production would still consist of 24 ODEs containing 35 parameters i.e. rate constants. Taking into account the linearity of the law of mass action (LMA) we can neglect the fast reactions and for this reason reduce the model to the rate limiting step.
| |
| - |
| |
| - | <br><br>
| |
| - |
| |
| - | <center>
| |
| - | <img width="733" height="643" src="https://static.igem.org/mediawiki/2010/6/68/Freiburg10_VirusProduction02.png" alt="reduced reaction scheme for the virus production" />
| |
| - | </center>
| |
| - |
| |
| - | <br><br>
| |
| - | <h3>Differential Equations</h3>
| |
| - | <center>
| |
| - | <img width="739" height="899" src="https://static.igem.org/mediawiki/2010/2/24/Freiburg10_VirusProduction03.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - |
| |
| - | <br><br>
| |
| - | <h2>Model for Virus Infection</h2>
| |
| - | <br><br>
| |
| - | <h3>Reaction Scheme</h3>
| |
| - | <center>
| |
| - | <img width="359" height="335" src="https://static.igem.org/mediawiki/2010/9/90/Freiburg10_VirusInfection01.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - | <br><br>
| |
| - | <h3>Reduced Reaction Scheme</h3>
| |
| - | <center>
| |
| - | <img width="359" height="227" src="https://static.igem.org/mediawiki/2010/8/83/Freiburg10_VirusInfection02.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - | <br><br>
| |
| - |
| |
| - | <center>
| |
| - | <img width="429" height="134" src="https://static.igem.org/mediawiki/2010/3/3f/Freiburg10_VirusInfection03.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - | <br><br>
| |
| - |
| |
| - | <h3>Differential Equations</h3>
| |
| - | <center>
| |
| - | <img width="655" height="314" src="https://static.igem.org/mediawiki/2010/8/85/Freiburg10_VirusInfection04.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - | <br><br>
| |
| - | <center>
| |
| - | <img width="800" height="285" src="https://static.igem.org/mediawiki/2010/8/84/Freiburg10_VirusInfection05.png" alt="Reaction scheme for the virus production" />
| |
| - | </center>
| |
| - |
| |
| - | </html>
| |
| - |
| |
| - | {{:Team:Freiburg_Bioware/Footer}}
| |
"
