The Study Of Fluctuation And Delay Effects In Gene Expression Process

Synthetic biology is a new branch of life sciences. We can take advantage of synthetic biological technology to construct a kind of artificial gene regulatory networks (GRNs) in biological systems, which are used for engineering applications or scientific researches. Genetic Toggle Switch is one of gene regulatory networks (GRNs), and it can present bistability or multistability. The study to Genetic Toggle Switch has both practical and theoretical important significance for understanding cellular unifonnization or differentiation.Genetic Toggle Switch involves the subcellular level biochemical reactions. On one hand, gene expression is a typical mesoscopic bioreactor system, where fluctuation effect is very significant. On the other hand, there is a vast separation of time scales during the expression process. For example, dimerization, protein-DNA binding/unbinding are typically the fast reactions and transcription, translation, degradation are the slow reactions. It is important to note that the transcriptional and translational processes are not just slow but also compound multistage reactions involving the sequential assembly of long molecules. These multistage processes should be treated as delayed reactions, in which the initiating events are separated from the appearance of products by certain interval of time delay. Thus, delay can not be ignored. Although one has studied the role of fluctuation for genetic switch stability dynamics, but the effect of delay on genetic switch stability dynamics is not very deep.In this thesis, we have investigated the effects of delay on dynamic behaviors of genetic toggle switch by the delayed stochastic simulation method. Three regimes (H-state, coexistence state, and L-state) have been present in the system, depending on the values of the transcription-factor binding rate. For coexistence state consisting of both H-state and L-state, one of them can be repressed by delay time, which results in a transition from coexistence state to the left state. A critical point (αc, τc) is found on the rate-delay time plane. With increasing binding rate, sequential transitions from H-state to coexistence state and further to L-state have been found for τ<τc, while only direct transition from H-state to L-state is left for τ>τc. Since transcriptional and translational delay is ubiquitous in gene regulatory networks, this may provide new insights into protein expression dynamics of genetic toggle switch.