Team:MIT

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This year, the MIT iGEM team is working to develop circuits that implement multiplexed cell-cell communication mediated by exosomes in mammalian cells. Our approach is to incorporate two parallel signaling strategies using exosomes: small miRNA and a Cas9 complex.
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In the first strategy, we utilize miRNA that are selectively targeted into exosomes. Sender cells produce exosomes with our miRNA signals. These exosomes carry signals to engineered receiver cells that use these miRNA inputs to modulate gene expression.  
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<h1>Motivation</h1>
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<p>This summer, the 2013 MIT iGEM team worked to engineer exosome mediated cell-cell communication. In vivo cell-cell communication is vital for pattern formation, organ development, coordinated responses to environmental changes, and the maintenance of an organism (Bacchus, 2012)</p>
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<h1>Our Contribution</h1>
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<p>We demonstrated that exosomes can be engineered to transport protein and miRNA signals of interest. These signals remain functional and can actuate a response in a receiver cell. By co-culturing sender and receiver cells, we have demonstrated exosome mediated unidirectional cell-cell communication. </p>
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<h1>Our Vision</h1>
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<p> Exosomes provide an innovative means of engineering cell-cell communication that can have exciting application in drug testing and development. Tissue engineers are currently working to develop organoids small tissue structures that recapitulate the behavior of organs in vitro  (Lancaster, 2013). Organoids can be used to test drugs more rigorously in a human-like context rather than relying solely on animal models. Thus drugs can be developed with a better understanding of their toxicity and efficacy. These multicellular structures require cell-cell communication, and our exosome mediated communication system could serve as an enabling technology for organoid development<p>
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<p> Lancaster, Madeline et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013)
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Bacchus, William et al. Synthetic two-way communication between mammalian cells. Nat. Biotechnol. 30, 991–996 (2012)
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</p>
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The second signaling strategy employs proteins contained within exosomes. We fuse targeting motifs to a CAS9-VP16 protein resulting in selective exosomal partitioning of this species in sender cells. In receiver cells, this signal modulates gene expression through the Cas9-CRISPR mechanism with a variable guide RNA.
 
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<h1>Sponsors</h3>
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| width=20% | [[Image:MIT_team.png|300px|Top|MIT Full Team]]
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  <li><a href="http://www.eecs.mit.edu/"><img src='https://static.igem.org/mediawiki/2011/2/22/Mit-eecs.jpg' /></a></li>
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  <li><a href="http://web.mit.edu/be/"><img src='https://static.igem.org/mediawiki/2011/a/a7/Mit-be.jpg' /></a></li>
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  <li><a href="http://web.mit.edu/cheme/"><img src='https://static.igem.org/mediawiki/2012/0/01/Cheme.png' style="width:175px"></a></li>
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  <li><a href="https://2012.igem.org/Main_Page"><img src='https://static.igem.org/mediawiki/igem.org/d/de/IGEM_basic_Logo_stylized.png' style="width:175px;"></a></li>
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<ul id="centersponsors" style="text-align:center">
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  <li><a href="http://www.geneious.com"><img src='https://static.igem.org/mediawiki/2011/6/65/Mit-geneious.jpg' /></a></li>
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  <li><a href="http://www.genewiz.com"><img src='https://static.igem.org/mediawiki/2011/3/33/Mit-genewiz.jpg' /></a></li>
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  <li><a href="http://www.addgene.org/"><img src='https://static.igem.org/mediawiki/2012/5/58/Addgene.png' /></a></li>
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  <li><a href="http://www.ll.mit.edu/"><img width="100%" src='https://static.igem.org/mediawiki/2013/6/6b/LL_Logo_blue.jpg' /></a></li>
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<li><a href="http://www.qiagen.com/"><img width="70%" src='https://static.igem.org/mediawiki/2013/0/0c/Qiagen-logo.GIF' /></a></li>
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<li><a href="http://gen9bio.com/"><img width="100%" src='https://static.igem.org/mediawiki/2013/3/33/Gen9logo.png' /></a></li>
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<ul id="rightsponsors" style="text-align:center">
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!align="center"|[[Team:MIT|Home]]
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  <li><a href="http://ebics.net"><img src='https://static.igem.org/mediawiki/igem.org/0/0d/EBICS_logo.JPG' style="width:175px"></a></li>
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!align="center"|[[Team:MIT/Team|Team]]
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  <li><a href="http://ehs.mit.edu/site/"><img src='https://static.igem.org/mediawiki/2012/5/52/Ehs_logo.jpg'></a></li>
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!align="center"|[https://igem.org/Team.cgi?year=2013&team_name=MIT Official Team Profile]
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  <li><a href="http://www.monsanto.com/Pages/default.aspx"><img src='https://static.igem.org/mediawiki/2012/1/18/Monsanto.png'></a></li>
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!align="center"|[[Team:MIT/Project|Project]]
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  <li><a href="http://www.idtdna.com/site"><img src='https://static.igem.org/mediawiki/2012/4/41/Idt2.png'></a></li>
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!align="center"|[[Team:MIT/Parts|Parts Submitted to the Registry]]
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  <li><a href="http://www.thirdrockventures.com/"><img width="100%" src='https://static.igem.org/mediawiki/2013/8/8d/Thirdrock.jpg'></a></li>
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!align="center"|[[Team:MIT/Modeling|Modeling]]
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  <li><a href="http://www.alnylam.com/"><img width="100%" src='https://static.igem.org/mediawiki/2013/c/c8/Alnylam-Pharmaceuticals-Inc-ALNY.png'></a></li>
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!align="center"|[[Team:MIT/Notebook|Notebook]]
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</ul>
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!align="center"|[[Team:MIT/Safety|Safety]]
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!align="center"|[[Team:MIT/Attributions|Attributions]]
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Latest revision as of 03:53, 29 October 2013

iGEM 2012

Motivation

This summer, the 2013 MIT iGEM team worked to engineer exosome mediated cell-cell communication. In vivo cell-cell communication is vital for pattern formation, organ development, coordinated responses to environmental changes, and the maintenance of an organism (Bacchus, 2012)

Our Contribution

We demonstrated that exosomes can be engineered to transport protein and miRNA signals of interest. These signals remain functional and can actuate a response in a receiver cell. By co-culturing sender and receiver cells, we have demonstrated exosome mediated unidirectional cell-cell communication.

Our Vision

Exosomes provide an innovative means of engineering cell-cell communication that can have exciting application in drug testing and development. Tissue engineers are currently working to develop organoids small tissue structures that recapitulate the behavior of organs in vitro (Lancaster, 2013). Organoids can be used to test drugs more rigorously in a human-like context rather than relying solely on animal models. Thus drugs can be developed with a better understanding of their toxicity and efficacy. These multicellular structures require cell-cell communication, and our exosome mediated communication system could serve as an enabling technology for organoid development

Lancaster, Madeline et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013) Bacchus, William et al. Synthetic two-way communication between mammalian cells. Nat. Biotechnol. 30, 991–996 (2012)

Sponsors

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