Team:Northwestern/Modeling

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Modeling

Overview

The purpose of our modeled system is to tune this system as a specific pH-sensing lysis device for releasing our phytase into the stomach. We aim to characterize the interaction between the H+/Cl- antiporter and the chloride-induced lysis cassette in our E. coli chassis. This model examines the effects of varied promoter strengths for the ClC-ec1 antiporter, as well as the plausibility of utilizing the system for nutritional purposes.

We start with a model cell that has entered the stomach. In this high pH environment, protons begin to leak into the cell. For our purposes, this flux of H+ ions into the cell is modeled by simple diffusion.

The leakage of protons due to the acidic environment begins to disrupt pH homeostasis. However, E. coli has acid resistance mechanisms in order to grow in low pH. One of these mechanisms is the ClC-ec1 antiporter protein, which pumps H+ out of the cell (against its gradient) by utilizing the chloride gradient. The flux of extracellular protons (He) into the cell as well as the production of the antiporter protein are illustrated below:

Each antiporter turnover moves one H+ out while importing two Cl-. We now begin by modeling with first order ordinary differential equations.

Variable Description Units
A_mRNA Messenger RNA for the ClC-ec1 antiporter concentration uM
A Antiporter protein concentration uM
Hi Intracellular proton concentration uM
He Extracellular proton concentration uM
Cli Intracellular chloride concentration uM
Cle Extracellular chloride concentration uM
rA (molar) transcription rate of A_mRNA within cell uM per second

Value Description Units
k1 A_mRNA degradation coefficient s-1
k2 A_mRNA to protein A translation rate coefficient s-1
k3 protein A degradation rate coefficient s-1
k4 antiporter kinetic coefficient /M3•s