Physical and functional map of the virus-induced Toll-like receptor signalling pathways

信号转导途径是由相互依赖的蛋白质组成的模块化复合物，它们以协调的方式将环境线索转化为表型反应。蛋白质纯化和蛋白质质谱的最新进展使得通过途径蛋白质组学对信号转导途径进行系统分析成为可能。与早期的方法不同，途径蛋白质组学方法允许对给定途径中的蛋白质-蛋白质相互作用进行公正和全面的研究，从而能够重建途径的连贯地图，并为对该过程的更多“系统生物学”理解奠定基础。病毒感染继续威胁着人类健康。虽然病毒看起来很简单，但抗病毒治疗基本上是不可用的。对病毒感染的先天免疫是由保守的分子模式如单链或双链RNA触发的。这些模式被不同的toll样受体（tlr）识别，启动i型干扰素的产生，从而建立抗病毒条件。该项目的目标是应用现代途径蛋白质组学技术，获得在病毒感染时触发干扰素产生的TLR信号通路的物理和功能图谱。

Signal transduction pathways are modular composites of interdependent sets of proteins that act in a coordinated fashion to transform environmental clues into a phenotypic response. Recent advances in protein purification and protein mass spectrometry have enabled the systematic analysis of signal transduction pathways by pathway proteomics. Unlike earlier approaches, the pathway proteomics approach allows for the unbiased and comprehensive investigation of protein-protein-interactions in a given pathway, thereby enabling the re-construction of a coherent map of the pathway and setting the ground for a more ¿systems biology¿ understanding of the process. Viral infections continue to threaten human health. Although viruses are seemingly simple, antiviral therapies are by and large unavailable. Innate immunity to viral infection is triggered by conserved molecular patterns such as single- or double-stranded RNA. Those patterns are recognized by distinct Toll-like receptors (TLRs) that initiate the production of type-I interferons, thereby establishing an antiviral condition. The goal of this project is to apply modern pathway proteomics technology to obtain a physical and functional map of the TLR signalling pathways that trigger interferon production upon viral infection.