Team:EPF Lausanne

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'''Taxi.Coli: smart drug delivery'''
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<br><br><br>
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We are proud to participate in iGEM 2013 and are excited to present<br>
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'''Taxi.Coli'''.
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<br>
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Taxi.Coli is a highly flexible and adaptable smart drug delivery system.<br>
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We want to use E.coli as a ''Taxi'', that expresses streptavidin on its surface as ''Seats'' for the ''Passengers'', which are the biotinylated nanoparticles that contain a drug. Once Taxi.Coli arrives at ''the Address'', a specific environment, it will produce an enzyme that degrades the nanoparticles, releasing the incorporated drug ''the passenger gets out of the car''. <br>Our effort will be limited to a proof of principle, but one can imagine a wide range of future applications.
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Taxi.Coli: smart drug delivery
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EPF_Lausanne’s team is proud to participate to iGEM 2013 and excited to present their project: Taxi.Coli: smart drug delivery. The team’s vision is to build a biosynthetic drug delivery concept. The key word of this project is “adaptability”. Our goal is to explore a way of using E.Coli as a highly modular carrier, opening the gate to several applications and alternatives in disease treatments. Using the principles of synthetic biology, we engineered a gelatinase secreting E. Coli able to bind gelatin nanoparticles using a biotin-streptavidin interaction and release them in a corresponding location. The drug delivery system is built in three parts: 1) the nanoparticle binding and 2) the environment sensing that 3) triggers the gelatinase release of the engineered E. Coli, liberating the content of the nanoparticle. The nanoparticles made of gelatin are able to carry any type of organic compound leading to a wide range of applications.
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<a href="https://2012.igem.org/Team:Slovenia/SafetyMechanisms"><img class="pic" src="https://static.igem.org/mediawiki/2012/a/a8/Svn12_homepage_2safety.png" width="300" height="300"/></a>
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<strong>Safety</strong>
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<p>In order to enable safe application of engineered cells in the microencapsulation based therapy we designed three safety mechanisms to <b>degrade the alginate capsules </b> at the end of the therapy, terminate the therapeutic cells by induction of apoptosis and to <b>tag any escaped cells for elimination</b> by the host's natural killer cells. <a href="https://2012.igem.org/Team:Slovenia/SafetyMechanisms">Read more...</a></p>
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==Achievements:==
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<a href="https://2012.igem.org/Team:Slovenia/Implementation"><img class="pic" src="https://static.igem.org/mediawiki/2012/3/3d/Svn12_homepage_3implementation.png" width="300" height="300" /></a>
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- We can produce biotinylated nanoparticles<br>
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- We can engineer E.coli expressing streptavidin (maybe even on the surface) to bind these nanoparticles<br>
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<strong>Implementation</strong>
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- We can engineer E.coli to sense different values of pH<br>
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<p>In <b>consultations with medical experts</b> we tailored our therapeutic devices based on implanted microencapsulated engineered cells to the treatments of hepatitis C and ischaemic heart disease by <i>in situ</i> <b>production of therapeutic protein effectors whose efficiency has already been demonstrated</b>. In agreement with our pharmacokinetic models, this strategy could <b>reduce side effects and improve efficiency of these therapies</b>. Switching between production of effectors with antiviral or anti-inflammatory and tissue regenerative effect could be regulated by administrating a small molecule inducer.
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- We can make E.coli express superfolded GFP constitutively<br>
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  <a href="https://2012.igem.org/Team:Slovenia/Implementation">Read more...</a></p>
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- We can excite other students about synthetic biology<br>
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Please also visit our [https://www.facebook.com/groups/EPFL.IGEM2013/ Facebook page]!
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<a href="https://2012.igem.org/Team:Slovenia/Modeling"><img class="pic" src="https://static.igem.org/mediawiki/2012/0/0a/Svn12_homepage_4modelling.png" width="300" height="300" /></a>
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<strong>Modeling</strong>
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<p>Modeling was used to simulate and improve the properties of the switch and the pharmacokinetic distribution of drugs in the tissue, which is required for an effective therapy and decreased side effects. We introduced <b>improved methods of switch simulations</b> such as a quantitative parameter derivation and algorithmic/mixed simulation that can capture mixed regulator binding to operators. We also included into the wiki a server <b>for online switch simulation</b>. A pharmacokinetic model of the local delivery of therapeutics by microencapsulated cells predicted that this type of drug delivery should have reduced systemic side effects.</p><p><b>Exhaustive modeling</b> of the switch <b>demonstrated that the classic genetic toggle switch arrangement is not stable without cooperativity</b>, but it <b>confirmed functionality and improved robustness of the our switch design</b> with <b>two positive feedback loops. This topology does not require cooperativity since nonlinearity is introduced by the positive feedback loop. <a href="https://2012.igem.org/Team:Slovenia/Modeling">Read more...</a></b></p>
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<a href="https://2012.igem.org/Team:Slovenia/Society"><img class="pic" src="https://static.igem.org/mediawiki/2012/f/fa/Svn12_homepage_5society.png" width="300" height="300" /></a>
 
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<strong>Society</strong>
 
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<p>Different aspects of general <b>medical applications of synthetic biology</b> and our project specifically <b>were discussed with a wide range of stakeholders, including medical professionals, patients</b>, experts on the law and ethics of GMO use and release, scientists, the media and the general public<b> that will all have to participate in a successful introduction of synthetic biology applications to clinical use</b>. We attempted to organize a <b>network of Slovenian high schools</b> to share the excitement of synthetic biology with <b>younger generations</b> and to demonstrate its application in <b>medicine and other fields</b>.  <a href="https://2012.igem.org/Team:Slovenia/Society">Read more...</a></p>
 
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<strong>Perspectives</strong>
 
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<li> We anticipate that designed DNA-binding element-based transcriptional factor logic will play a very important role in the development of synthetic biology,</li>
 
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<li>TAL-based switches allow simultaneous introduction of multiple switches to adopt multiple cellular states with numerous medical and other applications ,</li>
 
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<li><b>The safety</b> mechanisms, <b>including the inducible leak-free termination (prodrug), escape detection and capsule degradation components will allow implementation for different therapeutic purposes</b>,</li>
 
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<li>for an effective application <b>stable cell lines</b> containing integrated switches with selected therapeutic effectors and safety mechanisms will have to be established, most likely by the use of human artificial chromosomes,</li>
 
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<li>we plan to <b>initiate <i>in vivo</i> experiments</b> first <b>on ischaemia and wound healing</b>.</li>
 
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<p><a href="https://2012.igem.org/Team:Slovenia/Implementation">Read more...</a></p>
 
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<h2>Medal requirements</h2>
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<h3>Bronze medal</h3>
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  <li>We registered the team and had fun in the competition.</li>
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  <li>We filled in the Judging form.</li>
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  <li>We described our project using the iGEM wiki and our parts using the Registry of Standard Biological Parts.</li>
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  <li>We plan to present a poster and talk at the iGEM Jamboree in Lyon.</li>
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  <li>We designed and submitted the following Biobricks BBa_K1111001, BBa_K1111002, BBa_K111103, BBa_K1111004, BBa_K1111005, BBa_K1111006, BBa_K1111007, BBa_K1111008, BBa_K1111009, BBa_K1111010, BBa_K1111011, BBa_K1111012, BBa_K1111013, BBa_K1111014.</li>
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<h3>Silver medal</h3>
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  <li>We experimentally validated that the Biobrick BBa_K1111005 works as expected.</li>
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  <li>We documented all our parts on the iGEM Registry of Standard Biological Parts.</li>
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  <li>We investigated the safety issues which could be raised by our project. Take a look at our safety page.</li>
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<h3>Gold medal</h3>
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  <li>We improved the function of the already existing Biobrick BBa_K523013 by extensively characterizing and documenting it. This will help future teams to use it.</li>
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  <li>We prepared an amazing synthetic biology kit which will be used at public events and high school visits at EPFL. Take a look at our Outreach page. </li>
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<li>We organized a women and engineering's day at our university to promote women in science. </li>
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<h3>European Jamboree Results</h3>
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  <li>SILVER MEDAL</li>
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  <li>ADVANCE  TO WORLD CHAMPIONSHIP</li>
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== Thanks to our sponsors ==
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Many thanks to our sponsors who made it possible for us to take part in this amazing competition.
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[[File:Team-EPF-Lausanne sponso.jpg|center|550px]]
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Latest revision as of 00:06, 29 October 2013

Taxi.Coli: Smart Drug Delivery iGEM EPFL

Header




We are proud to participate in iGEM 2013 and are excited to present
Taxi.Coli.
Taxi.Coli is a highly flexible and adaptable smart drug delivery system.
We want to use E.coli as a Taxi, that expresses streptavidin on its surface as Seats for the Passengers, which are the biotinylated nanoparticles that contain a drug. Once Taxi.Coli arrives at the Address, a specific environment, it will produce an enzyme that degrades the nanoparticles, releasing the incorporated drug the passenger gets out of the car.
Our effort will be limited to a proof of principle, but one can imagine a wide range of future applications.





Project
Team
Safety
Outreach





Achievements:

- We can produce biotinylated nanoparticles
- We can engineer E.coli expressing streptavidin (maybe even on the surface) to bind these nanoparticles
- We can engineer E.coli to sense different values of pH
- We can make E.coli express superfolded GFP constitutively
- We can excite other students about synthetic biology



Please also visit our Facebook page!


Medal requirements

Bronze medal

  • We registered the team and had fun in the competition.
  • We filled in the Judging form.
  • We described our project using the iGEM wiki and our parts using the Registry of Standard Biological Parts.
  • We plan to present a poster and talk at the iGEM Jamboree in Lyon.
  • We designed and submitted the following Biobricks BBa_K1111001, BBa_K1111002, BBa_K111103, BBa_K1111004, BBa_K1111005, BBa_K1111006, BBa_K1111007, BBa_K1111008, BBa_K1111009, BBa_K1111010, BBa_K1111011, BBa_K1111012, BBa_K1111013, BBa_K1111014.

Silver medal

  • We experimentally validated that the Biobrick BBa_K1111005 works as expected.
  • We documented all our parts on the iGEM Registry of Standard Biological Parts.
  • We investigated the safety issues which could be raised by our project. Take a look at our safety page.

Gold medal

  • We improved the function of the already existing Biobrick BBa_K523013 by extensively characterizing and documenting it. This will help future teams to use it.
  • We prepared an amazing synthetic biology kit which will be used at public events and high school visits at EPFL. Take a look at our Outreach page.
  • We organized a women and engineering's day at our university to promote women in science.


    • European Jamboree Results

    • SILVER MEDAL
    • ADVANCE TO WORLD CHAMPIONSHIP



    Thanks to our sponsors

    Many thanks to our sponsors who made it possible for us to take part in this amazing competition.

    Team-EPF-Lausanne sponso.jpg



Wiki Links

Retrieved from "http://2013.igem.org/Team:EPF_Lausanne"