Team:MIT

From 2013.igem.org

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Revision as of 20:36, 9 August 2013

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.

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.

Our exosome communication system employs two complementary signaling strategies. We are engineering sender and receiver cell circuits for testing miRNA, recombinases, DNA-binding proteins, RNA-binding proteins, and proteases as signals. We are particularly excited about the possibility of multiplexed communication using an exosomally delivered Cas9-CRISPR system.

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.

We'd like to thank the following organizations for their support.

Home	Team	Official Team Profile	Project	Parts Submitted to the Registry	Modeling	Notebook	Safety	Attributions

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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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+<p style="line-height:200%">
-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.
+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.
+</p>
-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.
+<p style="line-height:200%;padding-top:10px">
+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.
+</p>
+<p style="line-height:200%;padding-top:10px">
+Our exosome communication system employs two complementary signaling strategies. We are engineering sender and receiver cell circuits for testing miRNA, recombinases, DNA-binding proteins, RNA-binding proteins, and proteases as signals. We are particularly excited about the possibility of multiplexed communication using an exosomally delivered Cas9-CRISPR system.
+</p>
+<p style="line-height:200%;padding-top:10px">
+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.
+</p>
+</div>
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