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研究生: 蔡怡君
Tsai, I-Chun
論文名稱: 白色念珠菌感染過程中之宿主-病源菌交互作用的重要功能性模組探討
Crucial Functional Modules Emerging in Host-Pathogen Interaction due to Candida Infection
指導教授: 陳博現
Chen, Bor-Sen
口試委員: 陳博現
莊永仁
藍忠昱
曾慶平
李曉青
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 65
中文關鍵詞: 白色念珠菌斑馬魚宿主-病源菌交互作用
外文關鍵詞: Candida albicans, zebrafish, host-pathogen interaction
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  • Introduction
    The clinical and biological significance of human fungal pathogen Candida albicans has been markedly increased since the Candida infection can cause lethal systemic infections. However, the defensive and invasive mechanisms of host-pathogen interaction are not elucidated as a whole. Therefore, the crucial functional modules emerging in C. albicans-zebrafish interaction are investigated.
    Results
    From a systems biology perspective, the early-stage and late-stage protein interaction networks for both C. albicans and zebrafish were constructed by the database mining and simultaneous host-pathogen interaction time-profile microarray, respectively. Based on the network reconfiguration and the Gene Ontology database annotation, the critical functional modules were identified for offensive and defensive mechanisms in infection process. Hyphal morphogenesis, small molecule and ion transport, protein secretion, and shift of carbon utilization functional modules of C. albicans are highlighted to play important roles in invasion and damage on host cells. On the other hand, immune response, apoptosis mechanism, ion transport and hemostasis-related process functional modules of zebrafish are found to be significant for defense or survival during Candida infection.
    Conclusion
    The crucial functional modules investigated by both host and pathogen microarray data at early and late stage of infection gain more insights into the molecular mechanisms of host-pathogen interaction during infection process. With the understanding of host-pathogen interaction and the identification of significant reconfiguration proteins in those crucial functional modules, efficient therapeutic strategies can be provided to combat against Candida infection.


    簡介
    由於白色念珠菌可造成致命、全身性的感染,因此,此種人類真菌病源菌在臨床及生物上的重要性已明顯地增加。然而,尚未有從整體的角度來解釋宿主-病源菌交互作用之間的攻擊和防禦機制,因此進行白色念珠菌-斑馬魚交互作用中的重要功能性模組之研究探討。
    結果
    從系統生物學角度來看,藉由資料庫探勘及隨實驗時間點推移同步所得的宿主-病源菌交互作用之基因晶片實驗數據,分別替白色念珠菌和斑馬魚建立出感染前期和後期的蛋白質交互作用網路。根據網路重組和基因功能註解,可辨認出在感染過程中的攻擊性和防禦性的重要功能性模組。白色念珠菌於入侵和損害宿主細胞時,菌絲形態發生、小分子和離子運輸、蛋白質分泌、碳利用轉換之功能性模組,扮演著重要的角色。另一方面,斑馬魚的功能性模組:免疫、細胞凋零、離子運輸、止血相關過程,對於斑馬魚面對念珠菌感染時的防禦或生存而言是重要的。
    結論
    藉由感染前期和後期的宿主和病源菌的基因晶片實驗數據,重要功能性模組得以研究,且增加了對於感染過程中宿主-病源菌交互作用的分子機制的理解。透過了解宿主-病源菌的交互作用以及辨認出重要的功能性模組中的蛋白質,可藉此提供有效的治療策略來對抗因白色念珠菌感染所造成的疾病。

    Content 1. Introduction 1 2. Materials and Methods 5 2.1 Data selection 5 2.2 Selection of protein pool 6 2.3 Protein interaction network construction 7 2.4 The network reconfiguration between early and late stages in infection process 12 2.5 Investigation of significant functional modules in infection process 14 3. Results 17 3.1 Construction of dynamic protein-protein interaction networks and investigation of significant proteins in Candida infection 17 3.2 Investigation of crucial functional modules emerging in Candida infection 19 3.2.1 Functional enriched modules of C. albicans in infection process 19 3.2.2 Functionally enriched subnetworks of zebrafish during Candida infection 26 4. Discussion 34 5. Conclusions 38 Bibliography 40

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