Team:NTU-LIHPAO-Taiwan/Modeling

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Modeling

Introduction

Noticing the problem of obesity growing in Taiwan, our team NTU-LIHPAO-Taiwan make efforts to improve a designed probiotic for oral peptide drug — “Healthin”. For preventing the side effects from commercial weight loss pills, as in our project design, the product CPP-PYY complex is produced by genetically modified Lactobacillus casei, which is orally ingested. TAT helps to penetrate through the villi, and the released PYY then binds to hypothalamus for appetite suppression.

In the Modeling part, we tried to simulate the pathways of our designed probiotic L. casei and secreted CPP-PYY complex inside human body, from oral ingestion to final PYY releasing, respectively. The ultimate goal is to build the general formula, and to find out the suitable and optimal dose for Healthin, which hopefully exerts the beneficial and harmless effect for appetite suppression.

In general, after taking Healthin, some L. casei pass through stomach and reach human intestine. Within the transient colonization, these modified L. casei produce CPP-PYY complex, and with the help of TAT, the complexes penetrate through the small intestine epithelial cells into circulation system. The linker between the complex is cut by thrombin in the blood, thus releasing free PYY for circulation, which binds to Y2 receptor in the hypothalamus for controlling satiety feeling. Moreover, the suicide device and bacteria survival were also considered in the simulation for safety concern. Combining data obtained from experimental results and several literatures, we applied MATLAB for calculation and simulation. By analyzing the pathways of L. casei inside human body step by step, the ultimate dose could be determined from the general formula.

Pathways

The pathways of the novel oral peptide drug Healthin consist of 5 parts, from intake through peptide release inside human body :

1. Bacteria distribution
2. CPP-PYY penetration efficiency
3. Absorption into bloodstream
4. Thrombin cleavage efficiency
5. Healthin drug effect

By utilizing MATLAB, we built a model from these pathways to construct the general formula for determining the dose response.

—>     [Click on here to see our Simulation Strategy and Results]

—>     [Click on here for Conclusion and Application]

[Fig.2-1] Pathway of Healthin

Maintained by the iGEM team NTU-LIHPAO-Taiwan    ©2015 NTU-LIHPAO-Taiwan