Difference between revisions of "Team:TecMonterrey GDL/Model"

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            <h1>Mathematical Model</h1>
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        <h1><img class="img-decorator2" alt="decoration2" src="https://static.igem.org/mediawiki/2018/3/3a/T--TecMonterrey_GDL--decoration1.png">Mathematical Model <img class="img-decorator" alt="decoration1" src="https://static.igem.org/mediawiki/2018/3/3a/T--TecMonterrey_GDL--decoration1.png"></h1>
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                        <h3> <span>For secretion peptides….</span> </h3>
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                          <br><br>
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                            <p>For future tests of the project in "Gut on a Chip" system, it is necessary to establish the optimal concentrations of nitrates needed to find the minimum concentration of the soluble transducer (sgp130) to inhibit transignaling.
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<h5 class="text-left"> For our project we will model the rates of fluorescence at which our secretion peptides express in response to variations in nitrosative stress. For this, we will use the following equation for our mathematical model: </h5>
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<br><br>For the prediction of the secreted concentrations of sgp130, a mathematical model was developed. This model relates the expressed protein concentration, secreted protein concentration, secretion rate, nitrate concentration and the rate of cell proliferation, where the cell line used needs IL6 to grow.
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<img align="center" src="https://static.igem.org/mediawiki/2018/f/f6/T--TecMonterrey_GDL--modelmath.png"> </img>
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<h5 class="text-left"> Where P1 represents the fluorescence of the secretion peptides and t the time; n is for the number of copies of mRNA, k1 expresses the specific rate of production per copy of mRNA and k2 represents the specific rate of secretion per unit of P1. </h5>
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                <br><br>
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                <h3>Molecular approach</h3>
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<h5 class="text-left"> Our model allowed us to construct a graphic relation between the fluorescence of our secretion peptides and the different concentrations of nitrate. Experiments were made in continuous culture, in which we added different concentrations of nitrate (CONCENTRACIONES) until steady state was reached and we measured the fluorescence with a plate reader (MODELO, AÑO…). The continuous system served to establish the secretion efficiency. </h5>
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<h5 class="text-left"> In general, this model was used to see the role played by the different concentrations of nitrate and thus be able to design an optimized system to stimulate the production of our proteins of interest . </h5>
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                <br><br>
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<h5 class="text-left"> We obtained the follow data showed in Table X, in Figure X we present the resulting curve of the fluorescence vs. the concentration of nitrate. </h5>
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                <h3>Simplified Model Of The Molecular Approach</h3>
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                <p>Simbiology model</p>
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                  <img class="img-responsive" src="https://static.igem.org/mediawiki/2018/5/58/T--TecMonterrey_GDL--Model--4.png" alt="service-image">
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                </center>
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                <br><br>
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                <p>Using Matlab’s 2018 Simbiology tool we designed the model presented on the top; where C1 is the complex formed by (IL6/sIL6R) and C2 is the complex formed by (IL6/sIL6R/sgp130)</p>
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                </div>
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<h6 class="text-left"> Table X. Data obtained at (CONDICIONES) of the fluorescence of the secretion peptides </h6>
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<h3 > imagen de tabla </h3>
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                <br><br>
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                <h3>Differential Equations Model</h3>
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                <p>A differential equations model is proposed where it is established that the proliferation of the HEPG2 cell line is a function of the concentration of nitrates, IL6, sIL6, sgp130, as well as, of the IL6 / sIL6 and IL6 / sIL6 / sgp130 complexes</p>
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                  <img class="img-responsive" src="https://static.igem.org/mediawiki/2018/2/2c/T--TecMonterrey_GDL--Model--6.png" alt="service-image">
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<h6 class= "text-left"> Figure X. Graphic of  the fluorescence of the secretion peptides against different concentrations of nitrate  at (CONDICIONES) </h6>
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<h3> imagen de figura </h3>
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                <h3>Simbiology model</h3>
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                <div class="col-md-6">
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                  <center>
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                  <img class="img-responsive" src="https://static.igem.org/mediawiki/2018/e/eb/T--TecMonterrey_GDL--Model--7.png" alt="service-image">
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                </center>
 
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<h4 align="center"> You can download the excel here </h4>
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                  <br><br><br><br><br>
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                  <p>It is based on the hypothesis that by increasing the concentration of nitrates,
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                    the ammount of NsrR protein bound to DNA will decrease. This will lead to an increase in the levels of sgp130
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                    synthesized that will bind to IL6/IL6R complex and thus, a decrease in the proliferation of the HEPG2 cell line will occurred.
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                    As can be seen in the figure presented in the left input parameters were obtained from literature.</p>
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            <br>
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                    <h4> <i>References:</i></h4>
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                  <br>
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                  <p style="text-align: justify">
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                    1. Crack JC, Svistunenko DA, Munnoch JT, Thomson AJ, Hutchings MI, Brun NEL. Differentiated, Promoter-specific Response of [4Fe-4S] NsrR DNA Binding to Reaction with Nitric Oxide*. In: The Journal of Biological Chemistry. ; 2016. doi:10.1074/jbc.M115.693192
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                  </p>
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                <p style="text-align: justify">
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                  2. Baran P, Hansen S, Waetzig GH, et al. The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling. J Biol Chem. 2018;293(18):6762-6775. doi:10.1074/jbc.RA117.001163
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                </p>
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              <p style="text-align: justify">
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                3. Han S, Machhi S, Berge M, Xi G, Linke T, Schoner R. Novel signal peptides improve the secretion of recombinant Staphylococcus aureus Alpha toxinH35L in Escherichia coli. AMB Express. 2017;7. doi:10.1186/s13568-017-0394-1
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              </p>
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Revision as of 09:08, 17 October 2018

TecMonterrey_GDL

Mathematical Model



For future tests of the project in "Gut on a Chip" system, it is necessary to establish the optimal concentrations of nitrates needed to find the minimum concentration of the soluble transducer (sgp130) to inhibit transignaling.

For the prediction of the secreted concentrations of sgp130, a mathematical model was developed. This model relates the expressed protein concentration, secreted protein concentration, secretion rate, nitrate concentration and the rate of cell proliferation, where the cell line used needs IL6 to grow.

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Molecular approach



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Simplified Model Of The Molecular Approach

Simbiology model



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Using Matlab’s 2018 Simbiology tool we designed the model presented on the top; where C1 is the complex formed by (IL6/sIL6R) and C2 is the complex formed by (IL6/sIL6R/sgp130)



Differential Equations Model

A differential equations model is proposed where it is established that the proliferation of the HEPG2 cell line is a function of the concentration of nitrates, IL6, sIL6, sgp130, as well as, of the IL6 / sIL6 and IL6 / sIL6 / sgp130 complexes



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Simbiology model

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It is based on the hypothesis that by increasing the concentration of nitrates, the ammount of NsrR protein bound to DNA will decrease. This will lead to an increase in the levels of sgp130 synthesized that will bind to IL6/IL6R complex and thus, a decrease in the proliferation of the HEPG2 cell line will occurred. As can be seen in the figure presented in the left input parameters were obtained from literature.


References:


1. Crack JC, Svistunenko DA, Munnoch JT, Thomson AJ, Hutchings MI, Brun NEL. Differentiated, Promoter-specific Response of [4Fe-4S] NsrR DNA Binding to Reaction with Nitric Oxide*. In: The Journal of Biological Chemistry. ; 2016. doi:10.1074/jbc.M115.693192

2. Baran P, Hansen S, Waetzig GH, et al. The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling. J Biol Chem. 2018;293(18):6762-6775. doi:10.1074/jbc.RA117.001163

3. Han S, Machhi S, Berge M, Xi G, Linke T, Schoner R. Novel signal peptides improve the secretion of recombinant Staphylococcus aureus Alpha toxinH35L in Escherichia coli. AMB Express. 2017;7. doi:10.1186/s13568-017-0394-1

4. Dumon-Seignovert L, Cariot G, Vuillard L. The toxicity of recombinant proteins in Escherichia coli: a comparison of overexpression in BL21(DE3), C41(DE3), and C43(DE3). Protein Expr Purif. 2004;37(1):203-206. doi:10.1016/j.pep.2004.04.025

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