Difference between revisions of "Team:NUS Singapore"

 
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{{NUS_Singapore}}
 
{{NUS_Singapore}}
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<body>
 
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<div id="slide">
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  <div class="slideshow-container">
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</div>
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    <div class="mySlides fade"> <img src="https://static.igem.org/mediawiki/2017/0/0c/NUS_2017_IGEM_slideshow.png"> </div>
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<!--<div class="newsflash-image-container">
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    <div class="mySlides fade"> <img src="https://static.igem.org/mediawiki/2017/d/d1/NUS_2017_IGEM_Group_Eng.jpeg"> </div>
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  <img src="#" alt="NUSGEM" width="1000" height="300">
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    <div class="mySlides fade"> <img src="https://static.igem.org/mediawiki/2017/0/04/NUS_IGEM_Groupphoto_1_tailored.jpeg"> </div>
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  <div class="center">Title</div>
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    <a class="prev" onclick="plusSlides(-1)">&#10094;</a> <a class="next" onclick="plusSlides(1)">&#10095;</a>  
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<!--**************************************** Project Description with Image Section ****************************************-->
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<div class="clear"></div>
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  <h1>Making Engineering of Customised Kill Switches Easier</h1>  
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<div class="column larger_section">  
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  <p>Many SynBio groups are engineering microbes that could one day be useful in detecting diseases, fighting cancer and monitoring heavy metals in rivers. However, engineered microbes may leak into the non-designated environment, posing threats to our natural ecosystem. This is a major hurdle towards the commercialization of engineered microbes. To address this, we need effective kill switches to prevent engineered microbes from escaping into the environment. However, existing kill switches have limitations and, more importantly, it is difficult to readily tailor make kill switches for different applications.</p><br>
 +
<p>
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Currently, there is no harmonized framework for kill switch design and construction. Team NUSgem aims to make engineering of such customised, effective kill switches easier. To this end, we are developing a library of characterized sensors, a killing and verification module which can be used in computer-aided design and modelling tool (such as <a href ="http://www.cellocad.org/"> CELLO</a> and <a href="http://advancesyn.com/"> AdvanceSyn Studio </a>) and can be readily modelled. As a proof of concept, we will focus on developing a kill switch for engineered probiotics for human health.</p>  
  
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<!--**************************************** Summary with Image Section ****************************************-->
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<p>
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<div class="column larger_section" style="float:left;margin-left:80px">
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We are a team of 6 undergraduates and 1 recent graduate student from different disciplines including Biomedical Engineering, Electrical Engineering, Science and Economics.</p>
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  <p>Recent advancements in engineered probiotics have enabled a host of novel medical therapeutics and diagnostics. One such example is scientists using engineered microbes to successfully target tumors in the gastrointestinal tract with minimal collateral damage and invasiveness [1, 2, 3, 4].Yet, despite these developments in engineered therapeutics, the risk of engineered microbes leaking into a non-designated environment remains an unresolved threat: a threat that could disrupt ecosystems and increase antibiotic resistance of natural bacteria. Therefore, critical to the feasibility of a functional engineered probiotic are control systems called killswitches that allow for spatial and temporal killing of the engineered probiotic once removed from its specific target site. However, the function of many existing killswitches is limited because they rely on: (1) Single input biosensors which decreases specificity [5]; (2) artificial amino acids which are difficult and unsuitable for implementation in the human body [6]; and (3) active control based on controlled expression of a toxin which in turn can lead to microbe survival upon mutagenesis of the killswitch [7, 8, 9].</p><br>
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−
  <p>To improve current switches, Team NUSgem proposes a novel passive biocontainment system for the human gut with enhanced specificity, safeguard and with a newly added function of verification . Our cascaded dual-biosensor killswitch is configured to achieve an OR gate logic upon detection of a physical (temperature) and chemical (phosphate) input to enhance specificity. Upon detection of a wastewater environment outside of the human body, the system will inhibit the expression of anti-toxin IM2, thereby allowing the constitutively produced toxin-endonuclease E2, to destroy the engineered probiotic. Our design purposefully places the E2 toxin gene in the probiotic’s genome to not only to create plasmid addiction of an IM2 plasmid, but also to safeguard against mutagenesis. Moreover, we use the bidirectional properties of the pTlpA36 temperature sensitive promoter to express the verification of engineered probiotic death. Added verifcation provides monitoring of the killswitch's effectivness which in turn, has the potential to used as a stimulus for a feedback-loop driven killswitch. </p>  
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  <img src="https://pbs.twimg.com/profile_images/792459490280865794/HjnMNi8H.jpg" alt="#" style="width:100%;height:300px;">
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    <img src="https://static.igem.org/mediawiki/2017/3/31/NUS_2017_IGEM_badbacteria.png">
 +
    <img src="https://static.igem.org/mediawiki/2017/6/6b/NUS_2017_IGEM_goodbacteria.png">
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</div>
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<div class="clear"></div>
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<!--**************************************** Video with Explanation Section ****************************************-->
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<div class="video_container">
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    <video controls poster="https://static.igem.org/mediawiki/2017/9/91/NUS_2017_IGEM_outline_cover.png">
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      <source src="https://static.igem.org/mediawiki/2017/6/6f/NUS_2017_IGEM_Videooverview.mp4" type="video/mp4">
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    </video>
 
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  <h1>Learn More</h1>
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<div class="polaroid" style="margin-left:80px">   
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<div class="polaroid">   
 
    
 
    
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   <img src="https://pbs.twimg.com/profile_images/792459490280865794/HjnMNi8H.jpg" alt="#" style="width:100%;display: block;height:180px">
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   <img src="https://static.igem.org/mediawiki/2017/5/56/NUS_2017_IGEM_home_interlab.png" alt="#" style="width:100%;display: block;height:180px">
 
    
 
    
 
   <div class="gallery-intro-container">
 
   <div class="gallery-intro-container">
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     <p>Interlab Study</p>
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     <a href="https://2017.igem.org/Team:NUS_Singapore/InterLab">INTERLAB STUDY</a>
 
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   <div class="gallery-overlay" style="background-color: #ffccbc">
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     <div class="gallery-overlay-text"><a href="#" target="_blank">Interlab Study</a></div>
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     <div class="gallery-overlay-text"><a href="https://2017.igem.org/Team:NUS_Singapore/InterLab">Interlab Study</a></div>
 
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   <img src="https://static.igem.org/mediawiki/2017/c/cc/NUS_2017_IGEM_home_modelling.png" alt="modelling" style="width:100%;display: block;height:180px">
 
    
 
    
 
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     <p>Modelling</p>
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     <a href="https://2017.igem.org/Team:NUS_Singapore/Model">MODELLING</a>
 
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Latest revision as of 16:07, 1 November 2017

Measurement Modelling Medal Check List
Team Member Attributions
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Silver Up Gold Integrated
Overview Methodology Kill Switch for Probiotics Kill Switch for BeeT
Description Interlab Study Parts Experiment Documentation Improvement Demonstrate Safety Future Works
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Making Engineering of Customised Kill Switches Easier

Many SynBio groups are engineering microbes that could one day be useful in detecting diseases, fighting cancer and monitoring heavy metals in rivers. However, engineered microbes may leak into the non-designated environment, posing threats to our natural ecosystem. This is a major hurdle towards the commercialization of engineered microbes. To address this, we need effective kill switches to prevent engineered microbes from escaping into the environment. However, existing kill switches have limitations and, more importantly, it is difficult to readily tailor make kill switches for different applications.


Currently, there is no harmonized framework for kill switch design and construction. Team NUSgem aims to make engineering of such customised, effective kill switches easier. To this end, we are developing a library of characterized sensors, a killing and verification module which can be used in computer-aided design and modelling tool (such as CELLO and AdvanceSyn Studio ) and can be readily modelled. As a proof of concept, we will focus on developing a kill switch for engineered probiotics for human health.

We are a team of 6 undergraduates and 1 recent graduate student from different disciplines including Biomedical Engineering, Electrical Engineering, Science and Economics.

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