Multicellular Analog Clock

Overview

Our concept of the multicellular analog clock is based on qualitative assumption such as how negative feedback loop behaves, how AHL diffuses, and so on. To ascertain our multicellular analog clock can function as an analogue clock, namely, to confirm the feasibility of our cell-cell communication included gene circuit, and to deepen understanding of behavior of the system, we conducted the following simulation.

Our model for multicellular analog clock consists of four parts: DDE analysis, parameter sensitivity analysis, parameter sweep, stochastic analysis. DDE analysis is to examine the feasibility of our project, and also provides the foundation for the other parts of analysis. Through parameter sensitivity analysis, we gained more insight of the relationship between input and output variables. The insight led to the third part of analysis, in which parameter sweep enabled us to grasp appropriate ranges fo the identified sensitive parameters. Finally, we conducted stochastic analysis with the sensitive parameters fixed, and simulate our device's behavior under the actual conditions.

DDE Model

To simulate the cell-cell communication system, we developed a delayed differential equation model. The equation used in the model are followings. The variables are described in the following table.

In our cell-cell communication system, the major kinetic events are: mCherry synthesis and degradation, LuxI synthesis and degradation, TetR synthesis and degradation, AHL synthesis and degradation. These kinetic events are contained in the equations. The following describes how the equations are developed.

• mCherry synthesis and degradation
• LuxI synthesis and degradation
• TetR synthesis and degradation
• AHL synthesis and degradation

RNA Silencing