Any biological system can be in essence viewed as a network. Systems Biology mainly studies hierarchical networks, and integrates the information of these networks into systematic knowledge of the entire network. However, the complexity of biological networks leads to two different kinds of research approaches: the one is top-down, i.e., simplifying a complex network into the one with lower complexity degree, and arriving at the understanding of the original network by studying these simple networks; the other is bottom-up, i.e., first studying fundamental building blocks of networks and then transitioning the study to more complex networks by the method of extending networks. The second research approach belonging to the category of synthetic biology has currently become a hot direction of Systems Biology. The relevant studies not only have a good perspective in biological pharmacy, artificial organs and genetic therapy fields but also provide important help for understanding many fundamental cellular processes.
There exist plentiful, relatively independent, function-specific network motifs in biological systems, which are small sub-networks repeatable and able to carry out specific biological functions. Just like electronic elements in engineering, network motifs can be connected to a more complex network. Recent studies have identified many functional motifs such as auto-regulatory network, positive feedback loop, and negative feedback loop as well as more complex motifs composed of these simple motifs, feed forward and feed forward loop as well as more complex motifs composed of these simple motifs. All these modules can carry out particular biological functions such as bistable switch, oscillation, excitability, filtering noise, signal transmission, signal amplification, stochastic focusing, and adaptation. In spite of diversity in the structure of networks carrying out these functions, they share some common properties, e.g., positive feedback loop is necessary to achieve bistable switch; negative feedback loop is essential for the generation of oscillation. From viewpoints of biological physics, revealing the structure and function of these simple networks and their composite modules is not only highly important for understanding regulatory mechansims of more complicated networks and even for understanding intracellular processes, but also greatly helpful for elucidating design principles of biological networks.
It has been verified that mathematical modeling is a strong tool of understanding the structure and function of network motifs. In mathematics, biological functions correspond in fact to particular dynamical behaviors, e.g., bistable switch corresponds to two stable steady states of a dynamical system of interest whereas an oscillation to a limit cycle. This thesis aims to study the relationship between the structure and the function of several common network motifs. By network building, mathematical modeling, theoretical analysis and numerical simulation, we investigate, from viewpoints of dynamics, stimulus-response relationship, functional robustness, information transmission, energy consumption and so on. Through such a systematic study, we try to conclude some general laws of common network modules.
The thesis is divided into five chapters with the main contents being as follows. Chapter 1 introduces first Systems Biology and then basic knowledge related to biological networks, including basic conceptions, research ideas, mathematical modeling methods, numerical simulation approaches, etc. In Chapter 2, we first introduce the classification of biological oscillators. Based on mechanisms of generating oscillations, we classify biological oscillators into smoothing oscillator, relaxation- type oscillator and stochastic oscillator. Then, we classify excitable systems into integrator and resonator, and reveal basic characteristics of these two classes of excitable systems. Finally, we study the tunabiity of an additional toggle switch in oscillatory and excitable systems, respectively. Chapter 3 focuses on the robustness and tunability of bistable switch. Through global and local robustness analysis, we find that the bistable robustness is related to the number and the type of the positive feedback loop. By studying the tunability of an additional toggle switch, we further find that this toggle switch can tune the bistable threshold but has little effect on the amplitude of the bistable switch. In Chapter 4, we first introduced a common signal transduction system: the two-component signaling network. Then, by investigating energy consumption and information transmission as well as the relationship between them, we find that information transmission may consume energy but also may not consume energy, depending on the network structure. In addition, we also investigate the relationship between the sensor structure and information transmission, and obtain some interesting results. In the final chapter, we first summarize the thesis, then discuss some unsolved issues on biological networks, and finally give the outlook of some potential yet related research directions.
| Date of Award | 3 Oct 2014 |
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| Original language | English |
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| Awarding Institution | - City University of Hong Kong
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| Supervisor | Hanxiong LI (Supervisor) |
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