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| − | <h2><i>“We will now discuss in a little more detail the Struggle for Existence...”</i></h2>
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| − | <h3 align = "right"<b><i>― Charles Darwin, The Origin of Species</i></b></h3>
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| − | <h1> Vanderbilt iGEM 2015 Project Description <h1>
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| − | <p>Every system that is genetically engineered harbors a potentially fatal vulnerability. The source of life's great diversity - spontaneous mutation - is for the synthetic biologist the source of constant apprehension and risk. The relentlessness of genetic mutation has discouraged attempts to treat it as anything other than unavoidable fact of tinkering with biology. Whether in a multifaceted genetic circuit or a simple protein expression platform, mutation is inevitable, and once it disrupts function, the organism will no longer experience the burden of transgene expression, causing the mutant to outcompete whatever has the intended sequence. Evolution and mutation work hand in hand to select against the maintenance of synthetic DNA sequences. Indeed, the mantra has been that time, in the form of mutation and evolution, will always find a way to erode and ultimately destroy everything that an engineer builds, no matter how ingeniously it may designed. </p>
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| − | <p>This year, here at Vanderbilt iGEM we are fighting back. We are proposing a novel approach based on rationally designed genomic architectures that promises to offer synthetic biologists unprecedented control over the evolutionary stability of their creations. At the heart of our strategy is an advanced computational algorithm that integrates decades worth of scientific data in order to identify and correct the highly-mutation prone 'hotspots' that lurk in every gene. Our strategy has a strong foundation in a rich literature from the fields of cancer biology and others that have annotated and characterized mutation hotspots for almost every conceivable source of mutagen, from ultraviolet radiation to recombination to polymerase errors. </p>
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| − | <p>When combined with synthetic DNA technology, our process becomes a simple and reliable optimization that is universally applicable to any coding gene being expressed in any organism. Our project first demonstrates the power of this rational synthetic gene design strategy by employing several canonical as well as highly original protocols for assaying DNA damage and its effects on the stability of artificial genetic elements. From these techniques, we can quantify everything from the selective subset of mutation types occurring on an in vitro level, up to how mutational loss of function translates at the scale of populations of genetically modified organisms. </p>
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| − | <p>To complement our work, we have harnessed our algorithm for use in what is becoming one of the most important tools for engineering biological molecules: directed evolution experiments. Not only can our engineered changes increase evolutionary stability in applications such as transgenic bioreactors, but it can also construct gene sequences that are more prone to mutate, thus accelerating studies into how to use evolutionary selection to produce tailored functional modifications to proteins. </p>
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| − | <p>Finally, we have investigated ways to build new genetically modified strains that exhibit greatly increased resistance to mutation. Combining our sequence-based strategies with the introduction of exogenous genes and removal of endogenous genes has enabled us to produce an expression platform for synthetic genes that not only has enhanced DNA repair mechanisms, but also has an entire artificial pathway introduced for the elimination of mutant strains from a population. </p>
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| − | <p>While any single engineered change to reduce mutation may still fail, when our innovative approaches to modulating evolutionary stability are taken in combination, they offer an unprecedented hope for taming evolutionary entropy. More than a victory for synthetic biology, we prove that through rational design principles- exactly what mutation most virulently tries to uproot- and with enough clever innovations, it is possible to defend against what seemed like an inevitability of nature. Score one for engineering. </p>
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| − | <h4> Editing your wiki </h4>
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| − | <p>On this page you can document your project, introduce your team members, document your progress and share your iGEM experience with the rest of the world! </p>
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| − | <p> <a href="https://2015.igem.org/wiki/index.php?title=Team:Vanderbilt&action=edit"> Click here to edit this page! </a></p>
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| − | <p>See tips on how to edit your wiki on the <a href="https://2015.igem.org/TemplatesforTeams_Code_Documentation">Template Documentation</a> page.</p>
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| − | <h4>Templates </h4>
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| − | <p> This year we have created templates for teams to use freely. More information on how to use and edit the templates can be found on the
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| − | <a href="https://2015.igem.org/TemplatesforTeams_Code_Documentation">Template Documentation </a> page.</p>
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| − | <h4>Tips</h4>
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| − | <p>This wiki will be your team’s first interaction with the rest of the world, so here are a few tips to help you get started: </p>
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| − | <li>State your accomplishments! Tell people what you have achieved from the start. </li>
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| − | <li>Be clear about what you are doing and how you plan to do this.</li>
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| − | <li>You have a global audience! Consider the different backgrounds that your users come from.</li>
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| − | <li>Make sure information is easy to find; nothing should be more than 3 clicks away. </li>
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| − | <li>Avoid using very small fonts and low contrast colors; information should be easy to read. </li>
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| − | <li>Start documenting your project as early as possible; don’t leave anything to the last minute before the Wiki Freeze. For a complete list of deadlines visit the <a href="https://2015.igem.org/Calendar_of_Events">iGEM 2015 calendar</a> </li>
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| − | <li>Have lots of fun! </li>
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| − | </ul>
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| − | <h4>Inspiration</h4>
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| − | <p> You can also view other team wikis for inspiration! Here are some examples:</p>
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| − | <li> <a href="https://2014.igem.org/Team:SDU-Denmark/"> 2014 SDU Denmark </a> </li>
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| − | <li> <a href="https://2014.igem.org/Team:Aalto-Helsinki">2014 Aalto-Helsinki</a> </li>
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| − | <li> <a href="https://2014.igem.org/Team:LMU-Munich">2014 LMU-Munich</a> </li>
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| − | <li> <a href="https://2014.igem.org/Team:Michigan"> 2014 Michigan</a></li>
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| − | <li> <a href="https://2014.igem.org/Team:ITESM-Guadalajara">2014 ITESM-Guadalajara </a></li>
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| − | <li> <a href="https://2014.igem.org/Team:SCU-China"> 2014 SCU-China </a></li>
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| − | </ul>
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| − | <h4> Uploading pictures and files </h4>
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| − | <p> You can upload your pictures and files to the iGEM 2015 server. Remember to keep all your pictures and files within your team's namespace or at least include your team's name in the file name. <br />
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| − | When you upload, set the "Destination Filename" to <code>Team:YourOfficialTeamName/NameOfFile.jpg</code>. (If you don't do this, someone else might upload a different file with the same "Destination Filename", and your file would be erased!)</p>
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| − | <a href="https://2015.igem.org/Special:Upload">CLICK HERE TO UPLOAD FILES</a>
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