Dynamics Modeling And Analysis Of Bistable Biological Systems

Bistability plays an important role in the development of biological systems.In order to better understand bistable systems and better regulate bistable systems existing in cancer cells,non-linear equations can be used to establish dynamics models of biological systems and perform quantitative and semi-quantitative analysis.Based on Hill function,this thesis explores the construction of bistability and analyzes bistable biological cases.In the aspect of constructing theoretical models,this thesis uses non-linear equations to describe positive and negative regulations between objects in each system.Because of few number of loops,this thesis enumerates all possible two-node structures.Because of large number of loops,this thesis enumerates some parts of three-node structures.If enumerated structure is bistable,this thesis explores the robustness of bistability and the law of parameter values for each eligible structure.Finally,on the basis of constructing two-node bistable system,this thesis not only finds the simplest structure which allows closed-loop three-node system to be bistable,but also proposes the basic rules to construct bistability in such a kind of three-node system and conjectures the law of constructing bistability in multi-node system.In addition,this thesis indicates that bistability has a strong heredity according to examples;it means that the existence of bistability or not and the characteristic of bistability in a multi-node,multi-loop superior system largely depends on the less-node,less-loop inferior system which is contained by superior system.More further,this thesis applies theoretical models to research drug-resistance which controlled by let7-LIN28 feedback loop during therapy of cancer and steady-states which controlled by let7-LIN28-OCT4 feedback loop during cancer metastasis.This thesis explores the stability of equilibrium points,bifurcation of system,and sensitivity of bistability to various parameters for each example and finds parameters which have a great impact on characteristic of system's bistability.Finally,this thesis performs kinetic simulation to entire systems.The results indicate that using dynamics models can analyze bistable biological systems very well andregulating key parameters in systems can effectively improve the environment of steady-states so that achieve the overall goals of resistance to drug-resistance and anti-metastasis.Therefore,constructing dynamics models on bistable biological systems has a horizontal future on application.