生物谷报道:据《自然》杂志本周报道,2006年12月8日蒙特利尔大学的研究人员和来自麻萨诸塞州立医院以及约翰斯霍普金斯大学的队友对免疫系统的一个基本方面有了重大突破性发现。他们首次采用系统的生物学方法创建了一个研究吞噬小体功能的模型。吞噬小体是一种细胞器,其功能是消灭侵入机体的病原体。尽管吞噬小体在正常人体免疫防御中发挥着重要作用,但是目前对其结构和功能我们知之甚少。
目前,传染病仍然是全球死亡病例的主要死因之一,每年抗生素耐药菌的增多使得情况变得更糟。可喜的是,由蒙特利尔大学细胞生物学和病理学系的教授Michel Desjardins,哈佛医学院教学医院——麻萨诸塞州立医院的医师Drs Lynda Stuart 和 Alan Ezekowitz,约翰斯霍普金斯大学生物医学工程实验室的博士Joel Bader带领的团队研制出的模型,将可以更好地阐明支配吞噬小体功能的复杂的细胞内相互作用。
研究人员运用基于蛋白组学和基因组学的方法来揭示各种感染的分子学上改变。这种方法将促进治疗方法和新疫苗的产生。研究人员通过研究像果蝇这样的简单生物,对和吞噬小体有关的超过600种蛋白质作了研究,再运用经典的细胞生物学联合蛋白组学,功能基因组学和计算分析的新方法,建立了一个这些蛋白质之间相互作用的详细模式图,这样可以认识以前未知的吞噬作用的调节和可能的免疫防御分子学路径。这个模型将有利于研究传染病,促进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.