Team:ETH Zurich/Model/In Silico Final

Simulated Behavior of Our Whole System In-Vivo

All our experimental and modeling efforts converge here.

Results

After fitting the model describing the behavior of our circuit on our experimental data, we simulated the response of our whole circuit including both versions A and B of our hybrid promoter to test their impact on our sensing circuit in the real-life scenario of tumor colonization and asses their performance.

Azu_PromoterA_Gif
Figure 1: Simulation showing our Hybrid promoter version A turning ON in case of Tumor colonization
Azu_PromoterB_Gif
Figure 2: Simulation showing our Hybrid promoter version B turning ON in case of Tumor colonization
Azu_PromoterA
Figure 1: Azurin concentration for the case of our hybrid promoter version A.
Azu_PromoterB
Figure 2: Azurin concentration for the case of our hybrid promoter version B.

Inference

Figures 1 and 2, show that both our promoters fully turn ON in case of High dcell and High [Lac]. From Figures 3 and 4, a substantial differentiation can be made between both hybrid promoters A and B.

The promoter B helps achieves a higher steady state of azurin concentration but is less specific as compared to promoter A, which exhibits a significantly higher fold-change from the low lactate, high cell density situation.

By choosing one promoter or the other, our bacterial system could therefore adapt to the specific needs of the clinical application. For our case, as azurin as been shown to be rather specific towards tumor cells, we might want to go for the promoter B. However, if we were to implement a more potent and less target cytotoxic agent, as previously suggested, we would definitely choose the promoter A.