生物谷報(bào)道：據(jù)《自然》雜志本周報(bào)道,，2006年12月8日蒙特利爾大學(xué)的研究人員和來自麻薩諸塞州立醫(yī)院以及約翰斯霍普金斯大學(xué)的隊(duì)友對(duì)免疫系統(tǒng)的一個(gè)基本方面有了重大突破性發(fā)現(xiàn),。他們首次采用系統(tǒng)的生物學(xué)方法創(chuàng)建了一個(gè)研究吞噬小體功能的模型,。吞噬小體是一種細(xì)胞器，其功能是消滅侵入機(jī)體的病原體,。盡管吞噬小體在正常人體免疫防御中發(fā)揮著重要作用,，但是目前對(duì)其結(jié)構(gòu)和功能我們知之甚少,。
目前,，傳染病仍然是全球死亡病例的主要死因之一,，每年抗生素耐藥菌的增多使得情況變得更糟?？上驳氖?，由蒙特利爾大學(xué)細(xì)胞生物學(xué)和病理學(xué)系的教授Michel Desjardins,，哈佛醫(yī)學(xué)院教學(xué)醫(yī)院——麻薩諸塞州立醫(yī)院的醫(yī)師Drs Lynda Stuart 和 Alan Ezekowitz，約翰斯霍普金斯大學(xué)生物醫(yī)學(xué)工程實(shí)驗(yàn)室的博士Joel Bader帶領(lǐng)的團(tuán)隊(duì)研制出的模型,，將可以更好地闡明支配吞噬小體功能的復(fù)雜的細(xì)胞內(nèi)相互作用。
研究人員運(yùn)用基于蛋白組學(xué)和基因組學(xué)的方法來揭示各種感染的分子學(xué)上改變,。這種方法將促進(jìn)治療方法和新疫苗的產(chǎn)生,。研究人員通過研究像果蠅這樣的簡(jiǎn)單生物，對(duì)和吞噬小體有關(guān)的超過600種蛋白質(zhì)作了研究,，再運(yùn)用經(jīng)典的細(xì)胞生物學(xué)聯(lián)合蛋白組學(xué),，功能基因組學(xué)和計(jì)算分析的新方法，建立了一個(gè)這些蛋白質(zhì)之間相互作用的詳細(xì)模式圖,，這樣可以認(rèn)識(shí)以前未知的吞噬作用的調(diào)節(jié)和可能的免疫防御分子學(xué)路徑,。這個(gè)模型將有利于研究傳染病，促進(jìn)形成新的抗病菌方案,。
英文原文：
A systems biology analysis of the Drosophila phagosome.
Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite the crucial role of phagosomes in immunity, their components and organization are not fully defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from the genetically tractable model organism Drosophila melanogaster and address the complex dynamic interactions between proteins within this organelle and their involvement in particle engulfment. Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these were organized by protein–protein interactions to generate the 'phagosome interactome', a detailed protein–protein interaction network of this subcellular compartment. These networks predicted both the architecture of the phagosome and putative biomodules. The contribution of each protein and complex to bacterial internalization was tested by RNA-mediated interference and identified known components of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis such as the 'exocyst', a macromolecular complex required for exocytosis but not previously implicated in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power of applying this approach to the study of complex cellular processes and organelles and expect that this detailed model of the phagosome will provide a new framework for studying host–pathogen interactions and innate immunity.
