Difference between revisions of "Team:New York City/Model"

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<h3>★  ALERT! </h3>
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<p>This page is used by the judges to evaluate your team for the <a href="https://2018.igem.org/Judging/Medals">medal criterion</a> or <a href="https://2018.igem.org/Judging/Awards"> award listed below</a>. </p>
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<p> Delete this box in order to be evaluated for this medal criterion and/or award. See more information at <a href="https://2018.igem.org/Judging/Pages_for_Awards"> Instructions for Pages for awards</a>.</p>
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                <div class="navbar-brand"><a href="https://2018.igem.org/Team:New_York_City">New York City iGEM</a></div>
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                <div class="collapse navbar-collapse" id="navbarSupportedContent">
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                    <ul class="navbar-nav mr-auto">
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                        <li class="nav-item dropdown">
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                            <a class="nav-link dropdown-toggle py-2 d-none d-md-inline-block" href="#" id="navbarPR"
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                                role="button" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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                                Project
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/HD">What is
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                                    Huntington's?</a>
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/Description">Description</a>
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/Design">Design</a>
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/Model">Model</a>
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/InterLab">InterLab</a>
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                                Human Practices
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                                    Practices</a>
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                                    Practices</a>
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/Collaborations">Collaborations</a>
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                                Team
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/Team">Team</a>
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                                <a class="dropdown-item" href="https://2018.igem.org/Team:New_York_City/Attributions">Attributions</a>
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        <h2 align="center">Model</h2>
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        <p class="lead">Our goal is to create a cure for Huntington’s Disease (HD) by developing a RNA strand
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            displacement technology that can target and block mutated huntingtin (HTT) mRNA strands and replace them
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            with corrected strands for proper protein synthesis. Since an increased number of CAG repeats in the HTT
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            gene coding for the polyglutamine tail characteristic of HD contributes to neurotoxicity in this disease,
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            we decided to find a cure for HD in the RNA level. Last year, we designed a modified plasmid consisting of
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            a chaperone strand and a corrected HTT mRNA strand using the software programs Vienna and mFold. The
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            chaperone strand contains a small RNAi like toehold sequence designed to bind to the hairpin loop sequence
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            of mutated HTT mRNA strands. Upon binding of the chaperone strand to the mutated mRNA strand, the corrected
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            HTT mRNA strand would be released into the cytoplasm for proper protein synthesis.</p>
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<h1> Modeling</h1>
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        <p class="lead">To design our modified plasmid, we first looked into various huntingtin (HTT) mutants and the
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            percentage of their occurrence in genetic databases, including NCBI. The goal was to identify hairpin loop
 +
            sequences in HTT mutants so that they could be targeted by the chaperone to achieve toehold strand
 +
            displacement of mutated HTT with a corrected strand. Then, we used the software programs mFold and Vienna
 +
            to model RNA sequence folds and to find a tractable hairpin within the 5’ UTR of HTT mutants. In addition,
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            we used the programs Genstrip and RNAI designer to review more sequences for us to target. Lastly, UGENE
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            was used to view and align all the sequences we reviewed, allowing us to target the most optimal hairpin
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            loop in HTT mutants with the toehold sequence within the chaperone strand in our modified plasmid.</p>
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    </div>
  
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<p>Mathematical models and computer simulations provide a great way to describe the function and operation of BioBrick Parts and Devices. Synthetic Biology is an engineering discipline, and part of engineering is simulation and modeling to determine the behavior of your design before you build it. Designing and simulating can be iterated many times in a computer before moving to the lab. This award is for teams who build a model of their system and use it to inform system design or simulate expected behavior in conjunction with experiments in the wetlab.</p>
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<h3> Gold Medal Criterion #3</h3>
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                <a href="https://www.facebook.com/HDResolution/"><i class="fab fa-facebook-f display-4"></i></a>
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Convince the judges that your project's design and/or implementation is based on insight you have gained from modeling. This could be either a new model you develop or the implementation of a model from a previous team. You must thoroughly document your model's contribution to your project on your team's wiki, including assumptions, relevant data, model results, and a clear explanation of your model that anyone can understand.
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<br><br>
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                <a href="https://twitter.com/HDNYC_iGEM"><i class="fab fa-twitter display-4"></i></a>
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The model should impact your project design in a meaningful way. Modeling may include, but is not limited to, deterministic, exploratory, molecular dynamic, and stochastic models. Teams may also explore the physical modeling of a single component within a system or utilize mathematical modeling for predicting function of a more complex device.
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                <a href="https://www.instagram.com/nyc_igem/"><i class="fab fa-instagram display-4"></i></a>
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Please see the <a href="https://2018.igem.org/Judging/Medals"> 2018
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Medals Page</a> for more information.
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<h3>Best Model Special Prize</h3>
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To compete for the <a href="https://2018.igem.org/Judging/Awards">Best Model prize</a>, please describe your work on this page  and also fill out the description on the <a href="https://2018.igem.org/Judging/Judging_Form">judging form</a>. Please note you can compete for both the gold medal criterion #3 and the best model prize with this page.
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You must also delete the message box on the top of this page to be eligible for the Best Model Prize.
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<h3> Inspiration </h3>
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Here are a few examples from previous teams:
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<li><a href="https://2016.igem.org/Team:Manchester/Model">2016 Manchester</a></li>
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<li><a href="https://2016.igem.org/Team:TU_Delft/Model">2016 TU Delft</li>
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<li><a href="https://2014.igem.org/Team:ETH_Zurich/modeling/overview">2014 ETH Zurich</a></li>
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<li><a href="https://2014.igem.org/Team:Waterloo/Math_Book">2014 Waterloo</a></li>
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Revision as of 02:44, 15 October 2018

Model

Our goal is to create a cure for Huntington’s Disease (HD) by developing a RNA strand displacement technology that can target and block mutated huntingtin (HTT) mRNA strands and replace them with corrected strands for proper protein synthesis. Since an increased number of CAG repeats in the HTT gene coding for the polyglutamine tail characteristic of HD contributes to neurotoxicity in this disease, we decided to find a cure for HD in the RNA level. Last year, we designed a modified plasmid consisting of a chaperone strand and a corrected HTT mRNA strand using the software programs Vienna and mFold. The chaperone strand contains a small RNAi like toehold sequence designed to bind to the hairpin loop sequence of mutated HTT mRNA strands. Upon binding of the chaperone strand to the mutated mRNA strand, the corrected HTT mRNA strand would be released into the cytoplasm for proper protein synthesis.

To design our modified plasmid, we first looked into various huntingtin (HTT) mutants and the percentage of their occurrence in genetic databases, including NCBI. The goal was to identify hairpin loop sequences in HTT mutants so that they could be targeted by the chaperone to achieve toehold strand displacement of mutated HTT with a corrected strand. Then, we used the software programs mFold and Vienna to model RNA sequence folds and to find a tractable hairpin within the 5’ UTR of HTT mutants. In addition, we used the programs Genstrip and RNAI designer to review more sequences for us to target. Lastly, UGENE was used to view and align all the sequences we reviewed, allowing us to target the most optimal hairpin loop in HTT mutants with the toehold sequence within the chaperone strand in our modified plasmid.