Team:USTC CHINA/Project/Background

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         <div class="basic-bar">
         <div class="basic-bar">
         <h1>Background</h1>
         <h1>Background</h1>
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         <h2>ONE:Why We Want to Design T-Vaccine?<h2>
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         <h2>2013, We Redefined Vaccine<h2>
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         <p>In our world, billions of people suffer from contagion, however, only part of them can be prevented by proper vaccine. Many disadvantages limit the usage of traditional vaccine especially in developing countries.<p>  
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         <p align="justify">In our world, billions of people are suffering from contagions while only parts of contagions can be effectively prevented by existing vaccines. The disadvantages of traditional vaccines, like  being produced and purified with strict requirements on temperature, have limited their application, especially in developing countries.<p>  
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         <h3>the Comparison of Different Vaccine Delivery Ways<h3>
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         <h3>The Comparison of Different Vaccine Delivery Ways<h3>
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         <img src="https://static.igem.org/mediawiki/2013/c/c1/Traditional_needles.png" width="600" height="375" />
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         <img src="https://static.igem.org/mediawiki/2013/d/d7/USTC_CHINA_Traditional_needles.png" width="600" height="375" /><p align="justify">One solution to the problems is making change in drug delivery and create an in situ expression system based on synthetic biology.This year, we designed a new biological transdermal vaccine patch called T-vaccine.<p>  
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        <img src="https://static.igem.org/mediawiki/2013/c/c3/Traditional_transdermal_methods.png" width="600" height="375" />
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        <img src="https://static.igem.org/mediawiki/2013/6/69/T-vaccine.png" width="600" height="475" />
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         <p>So the key to solve these problems is to create a new way to both decrease the cost and deliver vaccine harmlessly. That is what we are working for, T-Vaccine.<p>  
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         <img src="https://static.igem.org/mediawiki/2013/3/31/USTC_CHINA_advantages_T-vaccine.png" width="600" height="600" />
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         <h2>TWO:What We Are Trying To Do.<h2>
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         <p> This year, our project focused on a revolutionary vaccine delivery. We chose bacillus subtilis as chassis to establish a transdermal vaccine fresh secreting band-aid which consists of four engineering b.subtilis, each of them carries a gene circuit independently. By using an excellent transdermal peptide TD1, three of them could express a serious of fusion proteins(antigen, 2 kinds of adjuvants) which could penetrating the skin and work as traditional vaccine molecule. The fourth type of them is our “reporter” which could notify users whether the band-aid works well and when they could stick or tear off the patch. Moreover we designed a reliable suicide system in bacillus subtilis for the very first time in iGEM. So it would be OK if our users tear patches off and throw them away. Cheap and convenient, we just create a world without needle.<p>
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         <h2>THREE:How Can We Make it?<h2>
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         <h2>Design of Project<h2>
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         <h3>1. Everything was So Naive Before We Found TD1.<h3>
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         <p align="justify">This year, our project focused on a revolutionary vaccine delivery. We chose <i>Bacillus subtilis</i> as chassis to establish a transdermal vaccine fresh secreting band-aid which consists of four engineering <i>B.subtilis</i>, each of them carries a gene circuit independently. By using an excellent transdermal peptide TD1, three of them could express a series of fusion proteins(antigen, 2 kinds of adjuvants), which could penetrate the skin and work as traditional vaccine molecules. The fourth type is our "reporter" , which could notify users whether the band-aid works well and when they could stick or tear off the patch. Moreover, we designed a reliable suicide system in <i>B.subtilis</i> for the very first time in iGEM. Innovative and incredible, we plan to create a world without needles.<p>
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         <p>When this idea first stroke us, it seemed amazing that our dream is so naïve and unpractical. Above all, how can we make antigen get through the skin barrier? We refer to various transdermal methods, like Iontophoresis, Sonophoresis, Microneedle. They require special equipment and deal damage to skin. Our idea remained unrealistic until we find Transdermal peptide 1.<p>
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         <h2>How do we realize T-vaccine<h2>
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         <p>TD-1 is an eleven amino acid peptide, which can greatly facilitate macromolecule transdermal delivery through intact skin. This was first discovered by professor Wen Longping in our university and the results were published on Nature biotechnology.<p>
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         <h3>1. Transdermal Peptide 1:<h3>
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         <p align="justify">When this idea first stroke us, it seemed that our dream is too naive and unpractical.  
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The most obvious problem is to make antigen get across the skin barrier, and we looked up various transdermal methods, like Iontophoresis, Sonophoresis, Microneedles,all of which require special equipment and can harm skin. Our idea remained unrealistic until we find Transdermal peptide 1.<p>
 +
         <p align="justify">TD1 is an eleven amino acid peptide, which can greatly facilitate macromolecule transdermal delivery through intact skin. This was first discovered by professor Wen Longping in our university and the results were published on Nature biotechnology.<p>
         TD1 Sequence<br>
         TD1 Sequence<br>
         <img src="https://static.igem.org/mediawiki/2013/9/97/%E9%80%8F%E7%9A%AE%E8%82%BD%E5%BA%8F%E5%88%97.png" width="580" height="50" />
         <img src="https://static.igem.org/mediawiki/2013/9/97/%E9%80%8F%E7%9A%AE%E8%82%BD%E5%BA%8F%E5%88%97.png" width="580" height="50" />
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         <img src="https://static.igem.org/mediawiki/2013/a/a7/Nature.png" width="580" height="400" />
         <img src="https://static.igem.org/mediawiki/2013/a/a7/Nature.png" width="580" height="400" />
         <h3>2. the Principle of TD1:<h3>
         <h3>2. the Principle of TD1:<h3>
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         <p>The biggest challenge of penetrating the skin is epidermis of skin barrier. Traditional transdermal methods have to break the epidermis, though it maybe painless, the injury still have the potential of infection. On the contrary, TD1 is painless and harmless to skin, it could open the skin channels shortly, so not only molecules but also filobactivirus could penetrate the skin and go into the blood circulation system.<p>
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         <p align="justify">TD1 can greatly assist macromolecule transdermal delivery across intact skin. It creates a transient opening in the skin barrier, enabling macromolecule to reach systemic circulation.<p>
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        Filamentous Phage <br>
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         <img src="https://static.igem.org/mediawiki/2013/8/81/%E4%B8%9D%E7%8A%B6%E5%99%AC%E8%8F%8C%E4%BD%93.png" width="580" height="500" />
         <img src="https://static.igem.org/mediawiki/2013/8/81/%E4%B8%9D%E7%8A%B6%E5%99%AC%E8%8F%8C%E4%BD%93.png" width="580" height="500" />
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         Skin<br>
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         <p><strong>Phage Library Screening</strong></p><br>
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         <img src="https://static.igem.org/mediawiki/2013/2/27/Skin.png" width="580" height="500" />
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         <img src="https://static.igem.org/mediawiki/2013/5/5e/EGFP.png" width="580" height="350" />
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         eGFP Transdermal<br>
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         <p>With eGFP, we could visualize whether the TD1-eGFP has transmitted across the skin. Besides, we can easily see the path of TD1-eGFP.</p><br>
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        <img src="https://static.igem.org/mediawiki/2013/f/f6/Time_-GFP.png" width="580" height="500" />
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         <div class="basic-bar">
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         <h1>References</h1>
         <h1>References</h1>
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         <p>1. ...<br/>
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         <p align="justify" style="font-size:xx-small;">
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           2. ....
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1.Chen, Y.P., et al., Transdermal protein delivery by a coadministered peptide identified via phage display. Nature biotechnology, 2006. 24(4): p. 455-460.<br/>
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           2.Scharton-Kersten, T., et al., Transcutaneous immunization with bacterial ADP-ribosylating exotoxins, subunits, and unrelated adjuvants. Infection and Immunity, 2000. 68(9): p. 5306-5313.<br/>
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          3.Glenn, G.M., et al., Transcutaneous immunization: A human vaccine delivery strategy using a patch. Nature Medicine, 2000. 6(12): p. 1403-1406.<br/>
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          4.Zhang, T., et al., Transmembrane Delivery and Biological Effect of Human Growth Hormone Via a Phage Displayed Peptide In Vivo and In Vitro. Journal of Pharmaceutical Sciences, 2010. 99(12): p. 4880-4891.<br/>
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          5.Prausnitz, M.R. and R. Langer, Transdermal drug delivery. Nature biotechnology, 2008. 26(11): p. 1261-1268.<br/>
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          6.van Dijl, J.M., et al., Functional genomic analysis of the <i>Bacillus subtilis</i> Tat pathway for protein secretion. Journal of Biotechnology, 2002. 98(2-3): p. 243-254.<br/>
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          7.Ogasawara, N., Systematic function analysis of <i>Bacillus subtilis</i> genes. Research in Microbiology, 2000. 151(2): p. 129-134.<br/>
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         </p>
         </p>
         </div>
         </div>
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<div id="t1"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/Results">Results</a></div>
<div id="t1"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/Results">Results</a></div>
<div id="t2"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/Results">Basic Experiment</a></div>
<div id="t2"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/Results">Basic Experiment</a></div>
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<div id="t2"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/Results/FurtherWork">Further Work</a></div>
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<div id="t2"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/AdvancingWork">Advancing Work</a></div>
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<div id="t2"><a href="https://2013.igem.org/Team:USTC_CHINA/Project/FutureWork">Future Work</a></div>
<div id="t1"><a href="https://2013.igem.org/Team:USTC_CHINA/Parts">Parts</a></div>
<div id="t1"><a href="https://2013.igem.org/Team:USTC_CHINA/Parts">Parts</a></div>

Latest revision as of 03:40, 29 October 2013

Background

2013, We Redefined Vaccine

In our world, billions of people are suffering from contagions while only parts of contagions can be effectively prevented by existing vaccines. The disadvantages of traditional vaccines, like being produced and purified with strict requirements on temperature, have limited their application, especially in developing countries.

The Comparison of Different Vaccine Delivery Ways

One solution to the problems is making change in drug delivery and create an in situ expression system based on synthetic biology.This year, we designed a new biological transdermal vaccine patch called T-vaccine.

Design of Project

This year, our project focused on a revolutionary vaccine delivery. We chose Bacillus subtilis as chassis to establish a transdermal vaccine fresh secreting band-aid which consists of four engineering B.subtilis, each of them carries a gene circuit independently. By using an excellent transdermal peptide TD1, three of them could express a series of fusion proteins(antigen, 2 kinds of adjuvants), which could penetrate the skin and work as traditional vaccine molecules. The fourth type is our "reporter" , which could notify users whether the band-aid works well and when they could stick or tear off the patch. Moreover, we designed a reliable suicide system in B.subtilis for the very first time in iGEM. Innovative and incredible, we plan to create a world without needles.

How do we realize T-vaccine

1. Transdermal Peptide 1:

When this idea first stroke us, it seemed that our dream is too naive and unpractical. The most obvious problem is to make antigen get across the skin barrier, and we looked up various transdermal methods, like Iontophoresis, Sonophoresis, Microneedles,all of which require special equipment and can harm skin. Our idea remained unrealistic until we find Transdermal peptide 1.

TD1 is an eleven amino acid peptide, which can greatly facilitate macromolecule transdermal delivery through intact skin. This was first discovered by professor Wen Longping in our university and the results were published on Nature biotechnology.

TD1 Sequence
Title of Nature Letter About TD1

2. the Principle of TD1:

TD1 can greatly assist macromolecule transdermal delivery across intact skin. It creates a transient opening in the skin barrier, enabling macromolecule to reach systemic circulation.

Phage Library Screening


With eGFP, we could visualize whether the TD1-eGFP has transmitted across the skin. Besides, we can easily see the path of TD1-eGFP.


References

1.Chen, Y.P., et al., Transdermal protein delivery by a coadministered peptide identified via phage display. Nature biotechnology, 2006. 24(4): p. 455-460.
2.Scharton-Kersten, T., et al., Transcutaneous immunization with bacterial ADP-ribosylating exotoxins, subunits, and unrelated adjuvants. Infection and Immunity, 2000. 68(9): p. 5306-5313.
3.Glenn, G.M., et al., Transcutaneous immunization: A human vaccine delivery strategy using a patch. Nature Medicine, 2000. 6(12): p. 1403-1406.
4.Zhang, T., et al., Transmembrane Delivery and Biological Effect of Human Growth Hormone Via a Phage Displayed Peptide In Vivo and In Vitro. Journal of Pharmaceutical Sciences, 2010. 99(12): p. 4880-4891.
5.Prausnitz, M.R. and R. Langer, Transdermal drug delivery. Nature biotechnology, 2008. 26(11): p. 1261-1268.
6.van Dijl, J.M., et al., Functional genomic analysis of the Bacillus subtilis Tat pathway for protein secretion. Journal of Biotechnology, 2002. 98(2-3): p. 243-254.
7.Ogasawara, N., Systematic function analysis of Bacillus subtilis genes. Research in Microbiology, 2000. 151(2): p. 129-134.