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| + | <div style="text-align: center;"><img height="400px" width="360px" src="https://static.igem.org/mediawiki/2015/thumb/3/37/Iitm_igem_bac_resis.jpeg/300px-Iitm_igem_bac_resis.jpeg"></div> |
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| + | <h2 align="center"><font size="5" color="green"><b>Simulating Evolution</b></font><br></br><font size="3" color="green">to</font></h2> |
| + | <h2 align="center"><font size="5" color="green"><b>Tackle Antibiotic Resistance</b></font></h2> |
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− | <h2>The Problem</h2>
| + | <p>Hello! We're the iGEM 2015 team from IIT Madras, India. Welcome to our wiki page. We are trying to develop a system that can tackle the problem of antibiotic resistance. Read on to learn more!</p> |
− | <p>Our iGEM project aims to tackle the emerging problem of antibiotic resistance by leveraging | + | <br> |
− | the power of natural selection under selective pressure. It is known that higher exposure
| + | <p> Antimicrobial agents like antibiotics and other drugs have served us well for over 70 years. However, they have been used so widely and for so long that the microbes that were supposed to be killed by the antibiotics have adapted to them! Antimicrobial resistance is a serious issue today, and could grow to become even worse in the future. A WHO report in April 2014 states that:</p> |
− | to antibiotics leads to the resistance against that antibiotic in bacterial populations.</p> | + | |
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− | <p>Anti microbial peptides are small protein molecules that have been shown to have anti-microbial | + | <p class="highlightBox">"this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health."</p> |
− | activity. They are also also known to exhibit lower tendency to develop antibiotic resistance.
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− | Recently, However, it has also been reported that a prolonged exposure to anti-microbial peptides
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− | could also lead to the emergence of resistance in bacteria</p>
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− | <h2>Our Solution</h2> | + | <p>Our iGEM project aims to tackle the emerging problem of antibiotic resistance by leveraging the power of evolution and natural selection under selective pressure, and synthetic biology. |
| + | </p> |
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− | <p>Here, we come up with a solution to this problem. We will synthesize a bacterial system that:</p> | + | <br></br> |
− | <ol>
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− | <li> Senses the cell density of pathogenic bacteria</li>
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− | <li> Our system releases anti-microbial peptides which kill pathogens, when it has sensed high cell density</li>
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− | <li> As the population goes down we release a peptide that neutralizes the activity of anti-microbial
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− | peptides, resulting into a stress free environment.The stress-free environment would be favourable to
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− | the wild type compared to the mutants which have developed antibiotic resistance</li>
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− | <p>Most pathogenic microbes secrete quorum sensing (QS) molecules like AHL, AI-2 when present in high
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− | cell density. QS molecules are sensed by receptor proteins on the cell surface of pathogens. These
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− | signaling molecules help them in regulating their communal activities.</p>
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− | <p>In the lab, we will be using E.Coli DH5alpha strain as pathogenic model. DH5alpha does not secrete | + | <div style="text-align: center;"><img src="https://imgs.xkcd.com/comics/evolving.png"></div> |
− | quorum sensing molecules natively. Therefore, we will genetically modify E. coli DH5alpha strain to
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− | release Auto-Inducer-2, a signaling molecule.[Ref. 4] We do this so as to create a recombinant that
| + | <figcaption>This xkcd comic depicts the "evolution" of bacteria as observed by a Biologist <br> like in the game Pokémon. |
− | mimics many pathogenic bacterium that secrete quorum sensing molecules.</p>
| + | <a href="https://xkcd.com/1147/"> <i>Link to comic webpage</i></a></figcaption> |
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− | <p>We will be using Lactococcus lactis MG1363 strain as a receiver. It has a simple circuit to detect high and
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− | low cell density of pathogens and release the appropriate molecules. L. lactis activates the expression
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− | of Alyteserin (antu-microbial peptide) at high cell density and NAly (neutralizing anit-microbila peptide)
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− | at low cell density. The precise mechanism with the genes involved is explained below.</p>
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− | <p>At low cell density, luxP,luxQ,luxU receptor proteins act as kinases that results in the phosphorylation
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− | of luxO (luxO-P) that activates qrr1-5 sRNAs with the help of sigma54 RNAP subunit factor, qrr RNAs degrade
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− | the mRNA of LuxR which has been found to activate and repress a number of gene when expressed in the cell.[Ref. 3] </p>
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− | <p>While at high cell density, the same receptor proteins (LuxP,Q,U) acts as phosphatases which removes | + | </div> <!--This is the closing tag for content container --> |
− | the phosphate from LuxO-P and this results into the higher expression of LuxR gene.[Ref. 3]</p>
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− | <p>Through this project, we aim to investigate a few questions and hypothesis:</p>
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− | <ol> | + | |
− | <li> Is bacterial resistance a big cause of concern when using antimicrobial peptides?</li>
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− | <li> Are oscillations in cell population observed when our system is used? Are the oscillations damped?</li>
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− | <li> How effective is the activity of NAly in neutralising the effects of Alyteserin?</li>
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− | </ol>
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− | <!--
| + | {{Team:IIT_Madras_Footer_Final}} |
− | <h4>Before you start: </h4>
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− | <p> Please read the following pages:</p>
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− | <ul>
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− | <li> <a href="https://2015.igem.org/Requirements">Requirements page </a> </li>
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− | <li> <a href="https://2015.igem.org/Wiki_How-To">Wiki Requirements page</a></li>
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− | </ul>
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− | <div class="highlightBox">
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− | <h4> Styling your wiki </h4>
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− | <p>You may style this page as you like or you can simply leave the style as it is. You can easily keep the styling and edit the content of these default wiki pages with your project information and completely fulfill the requirement to document your project.</p>
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− | <p>While you may not win Best Wiki with this styling, your team is still eligible for all other awards. This default wiki meets the requirements, it improves navigability and ease of use for visitors, and you should not feel it is necessary to style beyond what has been provided.</p>
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− | </div>
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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:IIT_Madras&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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− | <ul>
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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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− | <ul>
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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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Hello! We're the iGEM 2015 team from IIT Madras, India. Welcome to our wiki page. We are trying to develop a system that can tackle the problem of antibiotic resistance. Read on to learn more!
Antimicrobial agents like antibiotics and other drugs have served us well for over 70 years. However, they have been used so widely and for so long that the microbes that were supposed to be killed by the antibiotics have adapted to them! Antimicrobial resistance is a serious issue today, and could grow to become even worse in the future. A WHO report in April 2014 states that:
"this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health."
Our iGEM project aims to tackle the emerging problem of antibiotic resistance by leveraging the power of evolution and natural selection under selective pressure, and synthetic biology.
This xkcd comic depicts the "evolution" of bacteria as observed by a Biologist
like in the game Pokémon.
Link to comic webpage