The Role Of Interlinked Positive And Negative Feedback Loops On Noise Propagation In Gene Regulation Networks

It is well known that noise is inevitable in gene regulatory networks due to the low-copy numbers of molecules and local environmental fluctuations. The prediction of noise effects is a key issue in ensuring reliable transmis-sion of information.Interlinked positive and negative feedback loops are essential signal transduction motifs in biological networks. Positive feed-back loops are generally believed to induce a switch-like behavior, whereas negative feedback loops are thought to suppress noise effects.This thesis presents studies showing the role of interlinked positive and negative feedback loop on the noise propagation, based on analyzing the Myc/E2F/MiR-17-92network, using frequency domain analysis and stochastic simulation. First, in Chapter1, we present the a miniview on complex network and the biological networks. And then, in Chapter2, the basic mathematical descriptions of gene regulation networks and the loop in the gene regulation networks are depicted.In Chapter3, by using the signal sensitivity and noise amplifica-tion to quantify noise propagation, we analyze an abstract model of the Myc/E2F/MiR-17-92network that is composed of a coupling between the E2F/Myc positive feedback loop and the E2F/Myc/miR-17-92negative feedback loop. The role of the feedback loop on noise effects is found to be dependent on the dynamic properties of the system. For the pro-tein module, when the system is in monostability or bistability with high protein concentrations, noise is consistently suppressed. However, the neg- ative feedback loop reduces this suppression ability or improves the noise propagation and enhances signal sensitivity. In the case of excitability, bistability, or monostability, noise is enhanced at low protein concentra-tions. The negative feedback loop reduces this noise enhancement as well as the signal sensitivity. For the miRNAs module, the noise is always sup-pressed, when the system stay at on-state, the negative feedback loop can reduce the suppression ability or enhance the noise propagation and the signal sensitivity, which are repressed by the negative feedback loop when the system stay at off-state.In all cases, the positive feedback loop acts contrary to the negative feedback loop. We also found that increasing the time scale of the protein module or decreasing the noise autocorrelation time can enhance noise sup-pression; however, the system’s sensitivity remains unchanged. Taken to-gether, our results suggest that the negative/positive feedback mechanisms in coupled feedback loop dynamically buffer noise effects rather than only suppressing or amplifying the noise.Finally, in Chapter4, we have made a summary of our research and a plan for our future study.