Team:MIT

From 2011.igem.org

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<h3>Tissues by Design</h3>
<h3>Tissues by Design</h3>
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<p>Our project focuses on genetically programming tissue self-construction to achieve specific patterns of cell differentiation (initially with fluorescence, ultimately with cell fate regulators). This is accomplished through our synthetic genetic circuits, which incorporate our engineered 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>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="https://static.igem.org/mediawiki/2011/d/d9/Simulation_Initial_Patterned.png" style="max-width:570px; margin-right:10px;"/></p></br>
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<p><img src="https://static.igem.org/mediawiki/2011/5/51/Simulation.jpg" style="max-width:800px; margin-right:10px;"/></p></br>
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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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<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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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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<div align="center"><iframe width="400" height="300" src="http://www.youtube.com/embed/rGOB0gMxf_8" frameborder="0" allowfullscreen></iframe></div>
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<br><p>Specifically, we've developed a modular juxtacrine cell-cell signaling platform, using Notch and Delta proteins. Below is an animation depicting showing the Notch-Delta interaction leading to the cleavage of the Notch intracellular domain, which enters the nucleus and leads to the expression of cadherins, which cause cells to adhere to similarly expressing cells.</p></br>
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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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<div align="center"><iframe width="400" height="300" src="http://www.youtube.com/embed/dbz4VegsJOw?rel=0&amp;hd=1" frameborder="0" allowfullscreen></iframe>
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<div align="col_center"><iframe width="420" height="315" src="http://www.youtube.com/embed/rGOB0gMxf_8" frameborder="0" allowfullscreen></iframe></div><br>
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Latest revision as of 04:03, 29 October 2011

Tissues by Design

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.



Above is the result of a simulation run, starting with undifferentiated cells and ending with a pattern.

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. 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.



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.

Sponsors

MIT Departments