Team:MIT

From 2013.igem.org

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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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<h3>Project Description</h3>
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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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Pharmaceutical companies rely on various non-human model systems to test the efficacy and toxicity of drug candidates in development. However, these systems may not be predictive of drug behavior in humans. To better predict drug behavior in human trials, a synthetic model that more closely mimics ''in vivo'' drug response is desirable. Better ''in vitro'' predictions of drug toxicity and efficacy may lead to safer, more effective therapies.
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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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One promising model under development is the introduction of genetic circuits to populations of cells to produce organoids. These synthetic systems are compositionally similar to organs and respond to external stimuli in a comparable manner. The formation and maintenance of these structures requires coordinated behavior between individual cells based on their local context. As a means to coordinating behavior, the 2013 MIT iGEM team is developing an exosome mediated cell-cell communication system for use in mammalian cells.
 
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Our exosome communication system employs two complementary signaling strategies. We are engineering sender and receiver cell circuits for testing signals including miRNA, recombinases, DNA-binding proteins, RNA-binding proteins, and proteases. We are particularly excited about the possibility of multiplexed communication using an exosomally delivered Cas9-CRISPR system.
 
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We believe this method can be employed as a generalizable platform for intercellular communication. In concert with other synthetic biology modules, this work may be used in the future for creating mammalian systems that perform distributed computing, undergo multistep differentiation, or form complex microstructures.
 
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  <h3>Sponsors</h3>
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  <h1>Sponsors</h3>
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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://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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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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