Team:NYMU-Taipei/modeling/m6

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New part:Target

Introduction

This part aims to simulate the circuit of the Target part, which will be turn on when S. mutans is too much or phage is unable to control the S. mutans quorum.

circuit圖

LuxI coding sequence is controlled by nlmC promoter and threshold terminator. When the quorum of S. mutans is too much, the LuxI will be expressed and generate AHL-synthase. LuxR, on the other hand, is generated by E. coli constitutively. The LuxR and AHL can form a complex that can activate the pLuxR promoter. In our design, pLuxR promoter in E. coli can activate the lysine protein that can kill S. mutans only.
We model this part to see how the circuit works if phage is unable to control the S. mutans quorum, so the initial state of comE, the molecule that triggers the nlmC promoter, has a certain amount, which means the S. mutans is out of control.

System

(1)$$\frac{d[\text{luxI mRNA}]}{dt}=P_{nlmC} \frac{[\text{comE}]^{n1}}{K_{d1}+[\text{comE}]^{n1}} (1-a)^x - K_{deg\_mluxI} [\text{luxI mRNA}]$$ $$\frac{d[\text{luxI}]}{dt}= K_{t1} [\text{luxI mRNA}] - K_{deg\_luxI} [\text{luxI}]$$ 1.  $P_{nlmC}$:max nlmC promoter activity
2.  $K_{d1}$:promoter-TF dissociation constant
3.  $K_{deg\_mluxI}$:luxI mRNA degradation
4.  $(1-a)^x$:terminator effect
5.  $K_{t1}$:Translation efficiency
6.  $K_{deg\_luxI}$:luxI degredation
7.  $n1$:hill coefficient
(2)$$\frac{d[\text{luxR mRNA}]}{dt}=P_{const} - K_{deg\_mluxR} [\text{luxR mRNA}]$$ $$\frac{d[\text{luxR}]}{dt}= K_{t2} [\text{luxR mRNA}] - K_{deg\_luxR} [\text{luxR}]-K_{on}[\text{AHL}]^2[\text{luxR}]+K_{off}[\text{AHLluxR}]$$ 1.  $P_{const}$:constitutive promoter activity
2.  $K_{deg\_mluxR}$:luxR mRNA degradation
3.  $K_{t2}$:Translation efficiency
4.  $K_{deg\_luxR}$:luxR degredation
5.  $K_{on}$: reaction rate of $\text{2AHL+luxR} \rightarrow \text{AHLluxR(complex)}$
6.  $K_{off}$: reaction rate of $\text{AHLluxR(complex)} \rightarrow \text{2AHL+luxR}$
(3)$$\frac{d[\text{AHL}]}{dt}= K_{AHL} [\text{luxI}] +2 K_{off}[\text{AHLluxR}] -2 K_{on}[\text{AHL}]^2[\text{luxR}] - K_{deg\_AHL}$$ 1.  $K_{AHL}$:synthesis rate of AHL by LuxI
(4)$$\frac{d[\text{AHLluxR}]}{dt}= K_{on}[\text{AHL}]^2[\text{luxR}] - K_{off}[\text{AHLluxR}]$$ 1. reaction of $\text{2AHL+luxR} \rightarrow \text{AHLluxR(complex)}$
(5)$$\frac{d[\text{lysine gene mRNA}]}{dt}=P_{luxR} \frac{[\text{AHLluxR}]^{n2}}{K_{d2}+[\text{AHLluxR}]^{n2}} - K_{deg\_mlys} [\text{lysine gene mRNA}]$$ $$\frac{d[\text{lysine protein}]}{dt}= K_{t2} [\text{lysine gene mRNA}] - K_{deg\_lys} [\text{lysine protein}]$$ 1.  $P_{luxR}$:max pluxR promoter activity
2.  $K_{d2}$:promoter-TF dissociation constant
3.  $K_{deg\_mlyx}$:lysine gene mRNA degradation
4.  $K_{t2}$:Translation efficiency
5.  $K_{deg\_lys}$:lysine protein degredation
6.  $n2$:hill coefficient

Result

Reference

New part2

method

result

Reference