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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 how to develop, when stem cells differentiation into various cell types, to when to die, as mutated or erroneous cells undergo apoptosis.

We decided to examine how cells make those decisions.

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

Design adapted from Sui Huang, 2009.

For instance, if state A produced 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 of course is a massive over simplification, as A and B in nature are likely transcription factors. Yet, it helps to visualize this switch as such.

(TOP) Human Blastocyst from early development. (LEFT) Human liver cells. (RIGHT) Human heart cells.

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 a novel form of gene regulation using activators as repressors.

Potential Applications

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.

Alternatively, 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 such as 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 either the A or B state, which would be indicated by their respective reporters. If both spike, it will remain in the AB and indicate an equilibrium.