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| − | {{:Team:Brasil-USP/Templates/HeadContent|C1=Modeling results|C2=Gene Expression}}
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| − | {{:Team:Brasil-USP/modeling/TemplateIndex}}
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| − | <html>
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| − | <div class="container jamboreh">
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| − | <p class="lead">
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| − | Here we show our models to predict gene expression from our main circuits using roxA and lcp. We also show a detailed study of the kill switch mechanism we have used.
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| − | <p class="lead">
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| − | The main process we want to model in this section is the expression and translation of the genes involved in our circuits. Qualitatively, this whole process is triggered by the attachment of an enzyme that synthesizes RNA, known as RNA polymerase (RNAP), to the DNA near a gene. Promoters contain specific DNA sequences such as response elements that provide a secure initial binding site for RNA polymerase and for proteins called transcription factors that recruit RNAP. Then, mRNA associated with that gene is generated which can then be translated into a protein by ribosomes. This second process (translation) is triggered when a ribosome binds at a special region, called Ribosomal Binding Site (RBS). At the end of the day, a protein is produced.
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| − | </p>
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| − | <p class="lead">
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| − | At this point, the protein might be in its function conformal structure or not. We will stop at this point for now and model this whole process from rather coarser level of details: we will simulate populations of mRNAs and proteins and predict their concentration over time. As a sneaky-peek of what is to come, this is the basic prediction of our model:
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| − | </p>
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| − | <img src="https://static.igem.org/mediawiki/2015/c/cc/Team-Brasil-USP_ModeliGEM_TitleResultDeterministic.png" class="grafico" />
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| − | <p>
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| − | Notice that when Rhamnose concentration (black line) drops, TetR also drops and HokD starts to be produced, killing the cell.
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| − | </p>
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| − | </div>
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| − | <div class="wikicontent">
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| − | <h1>Main objective</h1>
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| − | <p class="lead">
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| − | Before we start dwelling with our mathematical modeling, let's state what are our main objectives and goals with this model. We want to ...
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| − | </p>
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| − | <ul>
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| − | <li>predict protein/enzyme concentration</li>
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| − | <li>take into account Rhamnose concentration</li>
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| − | <li>...</li>
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| − | </ul>
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| − | <h1>Modeling with Differential Equations</h1>
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| − | <p class="lead">
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| − | As mentioned above, we want to model the gene expression. Fundamentally, RNA polymerase (RNAP) binds to a transcription factor and triggers the transcription of a gene into mRNA; subsequently, ribosomes starts the translation of that mRNA into a protein/enzyme. The schematics below summarizes it.
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| − | </p>
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| − | <img style="width: 800px; display: block; margin: 10px auto 10px auto;" src="https://static.igem.org/mediawiki/2015/8/83/Team-Brasil-USP_ModeliGEM_GeneExpression_Schematics.png" />
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| − | <p class="lead">
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| − | Each process is based on the combination of two elements: first, a RNAP and the gene; then, ribosome and mRNA. The simplest way to model such combinations and their products is to use a Dynamical Systems approach [1,2], similar to techniques employed in Population Dynamics [3]. For a introductory text on this subject, click here.
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| − | </p>
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| − | <h1>RoxA and Lcp Production</h1>
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| − | <p class="lead">
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| − | Particularly, we want to study . Let's define $P_{rham}(t)$ as the Rhamnose concentration as function of time. This will promote the expression of our circuit. The concentration of RoxA and Lcp proteins are $P_{r}(t)$ and $P_{\ell}(t)$, respectively.
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| − | </p>
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| − | <h1>Kill Switch: hokD</h1>
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| − | <h1>Fluctuation analysis</h1>
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| − | </div>
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| − | <hr class="fancy-line" />
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| − | </html>
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| − | {{:Team:Brasil-USP/Templates/Foot}}
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