臺灣博碩士論文加值系統

白色念珠菌的感染與念珠菌症是非常難治療並且在藥物治療上產生了一個很嚴峻的挑戰。這篇論文利用了白色念珠菌感染斑馬魚的過程中得到的不同時間點的microarray data，來建造出第一個白色念珠菌跟長菌絲有關的的動態蛋白質互動（PPI）網路和斑馬魚對抗感染的動態PPI網路和他們之間有可能的PPI連線網路，將這三種網路合在一起變成一個宿主和病原體互相攻防的整體網路。根據這個整體的網路，白色念珠菌調控型態轉變與菌絲生長的pathway可以被更進一步的研究。為了找出跟菌絲生長有關的重要蛋白質，我們根據不同感染的階段（附著和入侵）建立出兩個蛋白質網路接著比較這兩個網路找出哪些蛋白質的連線數變化最大。從這些重要蛋白質我們可以更清楚的瞭解菌絲的發展在感染的過程中扮演的角色。我們也可以利用同樣的方法建立出兩個不同感染的階段的斑馬魚動態蛋白質網路，來找出斑馬魚重要的防守蛋白質，還有透過我們建立出來的白色念珠菌與斑馬魚之間有可能的PPI連線網路，可以看出哪些蛋白質在感染的過程中影響力是最大的，進而找出哪些生物功能在他們的互動中扮演著重要的角色。這個整合性的感染蛋白質互動網路可以幫助我們瞭解白色念珠菌造成致病的分子機制和斑馬魚抵抗的分子機制，希望能夠對改進藥物治療方法與找出新的抗菌藥物有所幫助。

Candida albicans infections and candidiasis are difficult to treat and create very serious challenge in therapeutics. In this study, based on interactive time profile microarray data of C. albicans and zebrafish in infectious process, the protein-protein interaction (PPI) networks of C. albicans and zebrafish and the intercellular protein interaction network between host and pathogen are simultaneously constructed for the first time by dynamic interaction model, as an integrated intercellular invading and defensive cellular network in infectious process. According to the intercellular interaction network, the signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans are further investigated. For further inspection of important proteins of virulent hyphal growth as the pathogenesis of C. albicans, two stage cellular networks are also developed according to the different infection stages (adhesion and invasion) and are then compared each other to find hyphal growth subnetwork with the most changes of protein interactions (i.e. hubs) in hyphal growth. From these important protein hubs in the hyphal growth subnetwork, we can gain more insight into the pathogenic role of the hyphal development in infectious process. The important defensive proteins of zebrafish can also be obtained by using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network are included as an integrated infectious protein interaction network to help us understand the molecular mechanisms underlying the pathogenicity of C. albicans and the defense of host to improve medical therapy and facilitate the development of new anti-fungal drugs.

Content
Abstract i
Content iii
List of Figures iv
List of tables v
List of supplemental materials vi
Introduction 1
Materials and Methods 5
2.1 Overview of the process 5
2.2 Data selection and preprocessing 5
2.3 Selection of protein pool for rough PPI networks 7
2.4 Dynamic model of infectious cellular protein interaction network 9
2.5 Network parameter identification via time series microarray data 10
2.6 Determination of significant interaction pairs 12
2.7 Construct intercellular protein interactions between pathogen and host 13
Results 16
3.1 Construction of the integrated infectious intercellular PPI network 16
3.2 Inspection of the dynamic hyphal growth PPI network of C. albicans 19
3.3 Utilizing dynamic intercellular PPI networks to discuss which protein will play an important role in hyphal growth development 22
3.4 The intercellular protein interactions between Candida albicans and zebrafish in infectious processing 28
Discussion 31
Conclusion 36
Bibliography 38

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