Team:MIT

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<h3>Tissues by Design</h3>
 
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<p>Our project focuses on tissue self-construction to achieve specific patterns of cell differentiation (initially with fluorescence, ultimately with cell fate regulators) with genetic circuits. To accomplish this, we focused on three components: cell-cell communication pathways, intracellular information processing circuits, and cell-cell adhesion. Through engineered control of these mechanisms, we are investigating how programmed local rules of interactions between cells can lead to the emergence of desired global patternings.</p>
 
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<p><img src="http://2011.igem.org/wiki/images/5/51/Simulation.jpg" style="max-width:800px; margin-right:10px;"/></p></br>
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<a href="http://2012.igem.org/Team:MIT/Motivation#s2">
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<p>Above is the result of a simulation run, starting with undifferentiated cells and ending with a pattern.</p>
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  <img src="http://2012.igem.org/wiki/images/4/44/Mithomepage1.png" alt="Why make logic circuits with strand displacement?" style="border:1px solid black" width="250"/>
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<p>Specifically, for cell-cell signaling, we developed a modular juxtacrine platform, using Notch and Delta proteins. For intracellular information processing circuits, as a proof of concept, we build a 2-input AND gate. For cell-cell adhesion, the final output of our system, we used cadherin.
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<a href="http://2012.igem.org/Team:MIT/Motivation">
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Below is an animation depicting our project components. The cell-cell signaling of Notch-Delta interaction leads to the cleavage of the Notch intracellular domain, which enters the nucleus and after logic processing, expresses cadherins, which cause cells to adhere to similarly expressing cells.
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  <img src="http://2012.igem.org/wiki/images/5/52/Mithomepage3.png" alt="How does strand displacement work?" style="border:1px solid black" width="250"/>
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We developed software tools to model the behavior of our system. Below is a sample of a simulation of cells with genetic circuits and how they differentiate.
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<a href="http://2012.igem.org/Team:MIT/TheKeyReaction#SDbio">
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  <img src="http://2012.igem.org/wiki/images/d/dd/Mithomepage5.png" alt="Strand displacement reactions work in vivo!" style="border:1px solid black" width="250"/>
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<a href="http://2012.igem.org/Team:MIT/Sensing#sensing1bio">
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  <img src="http://2012.igem.org/wiki/images/8/81/Mithomepage4.png" alt="Sensing mRNA Levels using Strand Displacement" style="border:1px solid black" width="250"/>
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<a href="http://2012.igem.org/Team:MIT/NOTGate#NOTgate_designbio">
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  <img src="http://2012.igem.org/wiki/images/b/b7/Mithomepage6.png" alt="Strand Displacement NOT Gate Design" style="border:1px solid black" width="250"/>
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<a href="http://2012.igem.org/Team:MIT/CircuitProduction#shortRNAbio">
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  <img src="http://2012.igem.org/wiki/images/b/b0/Mithomepage2.png" alt="Making short RNAs in vivo to use in circuits" style="border:1px solid black" width="250"/><br/>
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<h3>Project Description</h3>
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<p>The limited availability of promoters, genes, and repressors, along with the difficulty in assembling and delivering large DNA plasmids bottleneck advances in sophistication of genetic circuits in mammalian systems. In contrast, sophistication of <i>in vitro</i> synthetic DNA circuits has grown exponentially through the mechanism of <a href="http://2012.igem.org/Team:MIT/Motivation">toehold-mediated strand displacement</a>. These circuits demonstrate digital logic with reliable, modular, and scalable behaviors and maintain a small base-pair footprint. </p> <p>
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The raw processing power of these strand displacement circuits has been trapped in the test tube, sequestered from the traditional protein-based sensing, processing, and actuation method of synthetic biology. With the adaptation of strand displacement-based information processing, the application space of synthetic biology circuits will become larger and more accessible. </p>
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Our project leverages strand displacement to create a processing technology that supports multi-input <b>sensing</b>, sophisticated <b>information processing</b>, and precisely-regulated <b>actuation</b> in mammalian cells. We designed and tested a novel <a href="http://2012.igem.org/Team:MIT/NOTGate">fully-functioning DNA NOT gate</a>, which enables complete logic operation. In addition, we used RNA strand displacement to <a href="http://2012.igem.org/Team:MIT/Sensing">sense cellular mRNA</a>. We also demonstrated our ability to <a href="http://2012.igem.org/Team:MIT/CircuitProduction#shortRNAbio">produce short RNAs</a> <i>in vivo</i>.
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Most importantly, we demonstrated that toehold-mediated strand displacement in RNA can occur in mammalian cells. This, combined with our feasibility studies outlined in the above paragraph, shows that <a href="http://2012.igem.org/Team:MIT/TheKeyReaction#iteration_2_invivo"><b>strand displacement is a viable information-processing technology</b></a>. We envision <i>in vivo</i> RNA strand displacement as a new foundation for scaling up complexity in engineered biological systems, with applications in biosynthesis, biomedical diagnostics and therapeutics.
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<h3>Sponsors</h3>
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  <li><a href="http://www.eecs.mit.edu/"><img src='http://2011.igem.org/wiki/images/2/22/Mit-eecs.jpg' /></a></li>
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  <li><a href="http://web.mit.edu/be/"><img src='http://2011.igem.org/wiki/images/a/a7/Mit-be.jpg' /></a></li>
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  <li><a href="http://web.mit.edu/cheme/"><img src='http://2012.igem.org/wiki/images/0/01/Cheme.png' style="width:175px"></a></li>
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  <li><a href="http://2012.igem.org/Main_Page"><img src='http://igem.org/wiki/images/d/de/IGEM_basic_Logo_stylized.png' style="width:175px;"></a></li>
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  <li><a href="http://www.alnylam.com"><img src='http://2012.igem.org/wiki/images/1/16/ALYNYAM.jpg' style = "width:175px;"'></a></li>
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  <li><a href="http://www.geneious.com"><img src='http://2011.igem.org/wiki/images/6/65/Mit-geneious.jpg' /></a></li>
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  <li><a href="http://www.genewiz.com"><img src='http://2011.igem.org/wiki/images/3/33/Mit-genewiz.jpg' /></a></li>
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  <li><a href="http://www.neb.com"><img src='http://2011.igem.org/wiki/images/4/4d/Mit-neb.jpg' /></a></li>
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  <li><a href="http://www.addgene.org/"><img src='http://2012.igem.org/wiki/images/5/58/Addgene.png' /></a></li>
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  <li><a href="http://www.genscript.com/"><img src='http://2012.igem.org/wiki/images/8/80/Genscript_logo2.jpg' /></a>
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  <li><a href="http://www.pfizer.com"><img src='http://upload.wikimedia.org/wikipedia/en/7/77/Pfizerlogo.gif' width=175></a></li>
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  <li><a href="http://ebics.net"><img src='http://igem.org/wiki/images/0/0d/EBICS_logo.JPG' style="width:175px"></a></li>
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  <li><a href="http://ehs.mit.edu/site/"><img src='http://2012.igem.org/wiki/images/5/52/Ehs_logo.jpg'></a></li>
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  <li><a href="http://www.monsanto.com/Pages/default.aspx"><img src='http://2012.igem.org/wiki/images/1/18/Monsanto.png'></a></li>
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  <li><a href="http://www.flagshipventures.com/"><img src='http://2012.igem.org/wiki/images/3/3c/VentureLabsLogo.jpeg' style="width:175px"></a></li>
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  <li><a href="http://www.thirdrockventures.com"><img src='http://2012.igem.org/wiki/images/c/ca/TRV.jpg' style="width:175px"></a></li>
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  <li><a href="http://www.idtdna.com/site"><img src='http://2012.igem.org/wiki/images/4/41/Idt2.png'></a></li>
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  <li><a href="http://www.cmea.com/team/team-karl-handelsman.php"><img src='http://2012.igem.org/wiki/images/f/f0/Karl_Handelsman_logo.png' width=175> </a></li>
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    <h3>Platinum Sponsors</h3>
 
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    <h3>Gold Sponsors</h3>
 
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    <h3>Silver Sponsors</h3>
 
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Latest revision as of 19:41, 25 June 2013

iGEM 2012
Why make logic circuits with strand displacement? How does strand displacement work? Strand displacement reactions work in vivo!
Sensing mRNA Levels using Strand Displacement Strand Displacement NOT Gate Design Making short RNAs in vivo to use in circuits

Project Description

The limited availability of promoters, genes, and repressors, along with the difficulty in assembling and delivering large DNA plasmids bottleneck advances in sophistication of genetic circuits in mammalian systems. In contrast, sophistication of in vitro synthetic DNA circuits has grown exponentially through the mechanism of toehold-mediated strand displacement. These circuits demonstrate digital logic with reliable, modular, and scalable behaviors and maintain a small base-pair footprint.

The raw processing power of these strand displacement circuits has been trapped in the test tube, sequestered from the traditional protein-based sensing, processing, and actuation method of synthetic biology. With the adaptation of strand displacement-based information processing, the application space of synthetic biology circuits will become larger and more accessible.

Our project leverages strand displacement to create a processing technology that supports multi-input sensing, sophisticated information processing, and precisely-regulated actuation in mammalian cells. We designed and tested a novel fully-functioning DNA NOT gate, which enables complete logic operation. In addition, we used RNA strand displacement to sense cellular mRNA. We also demonstrated our ability to produce short RNAs in vivo.

Most importantly, we demonstrated that toehold-mediated strand displacement in RNA can occur in mammalian cells. This, combined with our feasibility studies outlined in the above paragraph, shows that strand displacement is a viable information-processing technology. We envision in vivo RNA strand displacement as a new foundation for scaling up complexity in engineered biological systems, with applications in biosynthesis, biomedical diagnostics and therapeutics.



Sponsors