Team:uOttawa/project

From 2014.igem.org

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                 <h2>Results and Interlab Study form</h2>
                 <h2>Results and Interlab Study form</h2>
                 <a href="https://static.igem.org/mediawiki/2014/c/cd/Uo2014-interlab.pdf">Download</a> our interlab study form and results.
                 <a href="https://static.igem.org/mediawiki/2014/c/cd/Uo2014-interlab.pdf">Download</a> our interlab study form and results.
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                <h1>References</h1>
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                <p>Ellis, T., Wang, X., &amp; Collins, J. (2009). Diversity-based, model-guided construction of synthetic gene networks with predicted functions. Nature Biotechnology, 27(5): 465-471.</p><p>
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Wang, Y., Huang, C., Tung, S., &amp; Lin, Y. (2000). Competition with TATA Box-Binding Protein for Binding to the TATA Box Implicated in Human Cytomegalovirus IE2-Mediated Transcriptional Repression of Cellular Promoters. DNA and Cell Biology, 19(10): 613-619.</p><p>
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Brachman, C., Davies, A., Cost, G., Caputo, E., Li, J., Hieter, P., &amp; Boeke, J. (1998). Designer Deletion Strains derived from Saccharomyces cerevisiae S288C: A Useful set of Strains and Plasmids for PCR-mediated Gene Disruption and Other Applications. Yeast, 14: 115-132.</p><p>
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Balázsi, G., Van Oudenaarden, A., &amp; Collins, J. (2011). Cellular Decision Making and Biological Noise: From Microbes to Mammals. Cel,l 144(6): 910-925.</p><p>
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Huang, S. (2009). Reprogramming cell fates: Reconciling rarity with robustness. Bioessays, 31(5): 546-560.</p><p>
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Way, J., Collins, J., Keasling, J., &amp; Silver, P. (2014). Integrating Biological Redesign: Where Synthetic Biology Came From and Where It Needs to Go. Cell, 157(1): 151-161.</p><p>
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Dueber, J., Mirsky, E., &amp; Lim, W. (2007). Engineering synthetic signaling proteins with ultrasensitive input/output control. Nature Biotechnology, 25(6): 660-662.
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</p><p>Huang S, Guo YP, May G, Enver T. “Bifurcation dynamics in lineage-commitment in bipotent progenitor cells.” Developmental Biology (2007). 305:695-713.</p>
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Revision as of 18:26, 17 October 2014

The Project

Engineering Fate: Cellular decision making and the Tri-Stable switch

Throughout our lives individual cells make vital decisions that directly affect us. From deciding what to become, to when to die.

We decided to examine how cells make those decisions.

It was hypothesized that a unique tri-stable switch controlled stem cell differentiation, where the three states are an arbitrary state A, B and a unique state where both states coexists stably (AB).

Design adapted from Sui Huang, 2009.

For instance, if A was making blue marbles and B red marbles, the three states would look like this:

Now instead of marbles, lets image A and B as cell types like liver cells and heart cells, and the AB state the undifferentiated state!

This is a primary example of cellular decision making. The 2014 uOttwa iGEM team chose to build this decision making pathway. To do so we created novel form of gene regulation, using activators as repressors.

Why build such a system? Understanding how this genetic network works and being able to model its behaviour may shed light on how exactly stem cells differentiate. More importantly, it will allow us to engineer cells that implement this synthetic decision-making pathway, and use it in an application such as logic gates.

Or, we may use this system as a unique cellular detector. If A and B are reporters driven by promoters that are sensitive to small molecules like phosphorous and nitrogen, these cells can monitor the balance between those two. The balance between those two is an important indicator of human pollution, which is indicated by high levels of phosphorous. If one spikes higher than the other, the cell will enter an A or B state, giving an indicator. If both spike, it will remain in the AB and indicate an equilibrium.