Difference between revisions of "Team:Washington/Modeling"

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<p> For the aptamer system, we constructed a time-dependent ODE model for protein expression resulting from an aptazyme-based genetic pathway (1). It describes the level of protein expression over time as a function of various system parameters, including transcription, aptazyme folding and cleavage, translation and degradation of RNA fragments and proteins. </p>
 
<p> For the aptamer system, we constructed a time-dependent ODE model for protein expression resulting from an aptazyme-based genetic pathway (1). It describes the level of protein expression over time as a function of various system parameters, including transcription, aptazyme folding and cleavage, translation and degradation of RNA fragments and proteins. </p>

Revision as of 02:48, 19 September 2015



Modeling

In our project we developed a novel paper microfluidic device for accomodating two biological detection systems. Both for the paper device and the apatazyme detection system, we constructed computational models to provide a theoretical framework for our experimental findings.

Paper Device

To model the functionality of the paper device, we developed a spatial model for fluid forces on a strip of paper and implemented it in COMSOL. The model simulates the material properties of the paper used in our experiments – represented by a rectangular prism – while submerged in fluid. We were able to calculate the magnitude of the fluid forces on the paper over time, which allowed insights on the influence of fluid forces on the device’s structural integrity.

Aptazyme

For the aptamer system, we constructed a time-dependent ODE model for protein expression resulting from an aptazyme-based genetic pathway (1). It describes the level of protein expression over time as a function of various system parameters, including transcription, aptazyme folding and cleavage, translation and degradation of RNA fragments and proteins.

(Carothers 2011)

We implemented the model in Python using Tellurium (2) and theoretically predicted results for various conditions. A comparison with literature data indicated a good fit between the computational model and the experimental setting.

The experimental ratio between the steady-state expression levels of the RED13 and RED6 plasmids is 1.21. In our model, the ratio is 1.30. The model accurately reproduces the experimentally determined relative levels of aptazyme activity.

References

(1) Carothers JM et. al. (2011): Model-Driven Engineering of RNA Devices to Quantitatively Program Gene Expression; Science, vol. 334(6063), pp. 1716-1719

(2) Tellurium. Python enviroment for Systems Biology developed and maintained at UW Seattle. (http://tellurium.analogmachine.org)