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Team:Freiburg Bioware/Modelling
From 2010.igem.org
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<h3>Reaction Scheme</h3> | <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> | 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 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> | + | 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> |
| - | Finally the recombinant viruses are released into the extracellular matrix and can be harvested for transduction. | + | 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. | ||
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<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" /> | <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" /> | ||
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<h3>Differential Equations</h3> | <h3>Differential Equations</h3> | ||
Revision as of 17:16, 21 October 2010
Modeling
For the modeling part we considered three main parts:- the virus production
- the infection of a target cell
- the therapy
Model for Virus Production
Reaction Scheme
Reducing the complexity of virus production we divide the cell into three compartments: the extracellular matrix (all quantities with the index ext), the cytoplasm (cyt) and the nucleus (nuc). Four plasmids are transfected - the plasmid coding for the helper proteins (helper), the gene of interest (goi) and two types of plasmids coding for the capsid proteins (capwt [wild type], capmod [modified]).The plasmids are transported into the nucleus where gene expression is initiated. Processed mRNA is transported into the cytoplasm and proteins (phelper, pcapwt, pcapmod) 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.
The gene of interest is replicated by cellular polymerases and single stranded DNA (ssDNA) is encapsidated into the preformed capsids (capsid) forming infectious viral particles (V).
Finally the recombinant viruses are released into the extracellular matrix and can be harvested for transduction.
Reduced Reaction Scheme
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.
Differential Equations
Model for Virus Infection
Reaction Scheme
Reduced Reaction Scheme
Differential Equations
