Team:KAIT Japan/Collaborations

collaborations

-Modeling collaboration-

Our team collaborated with iGEM 2016 team Tokyo_Tech(Tokyo Institute of Technology).
We requested help from them to create a mathematical model for our project. We felt so thankful to our collaborator for bring such strong contribution to our project.
In our project, we planned on increasing the production of Bacterial Cellulose (BC) produced by the bacteria A. xylinum. To increase the production of Bacteria Cellulose, we take the cellulose synthesis pathway into account.



Fig 1. Cellulose synthesis pathway of Acetobacter Based on the mechanisms of this pathway,


We planned to increase the amount of the production of cellulose by decreasing the amount of G6PDH and PGI enzymes by using the antisense method. In order to create a mathematical model for our project, team Tokyo_Tech took the principal reactions taking place in this production into account.

When antisense genes are expressed, an mRNA molecule is produced that is a mirror image of the targeted gene. The two, opposite mRNAs bind to one another, disrupting their function and making protein synthesis impossible. In effect, the targeted gene is blocked and transcription is prevented.
Therefore, we are using the antisense method to prevent the production of the enzymes G6PD and PGI. So, by representing the binding of the antisense mRNA to the nucleotide sequence with a Hill equation, they got the equation below.

Where αn,Kn and nn are constants from the Hill equation, And the concentration of the mRNA depends on the conditions of the experiment.
After applying the mathematical model above, they got the following graphs.

(a) Concentrations without applying the antisense method
(b) Concentration while inhibiting G6PD enzyme
(c) Concentrations inhibiting PGI enzyme
(d) Concentrations inhibiting both G6PD and PGI enzymes
(e) Concentrations strongly inhibiting both enzymes
The graph above shows that the more we inhibit the enzymes G6PD and PGI, the more the production of BC increases. Therefore, we can assume this model is correct. However, we cannot assume that this is the most appropriate result since it has not been corroborated with the experiments.

At last, we would like to thank our collaborator (Tokyo_Tech) once again for helping us in our initial stage of our project.
Tokyo_Tech