Investigation into the role of host-pathogen molecular interactions in animal diseases by microscopy and live cell imaging

动物卫生研究所(IAH)是世界领先的牲畜传染病研究中心。IAH致力于牛和家禽的几种主要病原体的研究，拥有研究自然宿主疾病的极好基础设施。IAH最近在转录组分析、蛋白质组学和生物信息学等领域投入了大量资金，以支持在动物重要疾病中研究复杂病原体-宿主相互作用的研究工作。这些最新的进展在IAH内部产生了越来越多的需求，以掌握细胞生物学，特别是利用最新的生物成像技术精确确定宿主和病原体蛋白的细胞定位的方法。荧光显微镜图像分析正在成为可视化病原体感染期间细胞内网络的动态和分子宿主-病原体相互作用的强大工具。目前的提议是获得资金，为康普顿实验室购买一台新的共焦显微镜，以便在不同的小组中开展各种病原体的研究项目。一些将受益于共焦显微镜的研究项目有：(A)鸡的马立克氏病，以检查MDV和宿主在细胞间传播的复杂相互作用，以及羽毛毛囊上皮支持无细胞病毒生产的独特能力；(B)分析细菌III型分泌的效应蛋白的谱带和功能；(C)柔嫩艾美耳球虫的宿主细胞入侵；(D)牛分枝杆菌肉芽肿的细胞类型动态和相互作用(E)冠状病毒-宿主蛋白(F)禽树突状细胞的生物学；(G)研究鸡的Toll样受体的作用。具有活细胞成像设备的共焦显微镜的可用性对于许多这些项目的成功以及对几种病原体与其自然宿主的分子相互作用的基本了解至关重要。

Institute for Animal Health (IAH) is a world-leading centre of excellence for research into infectious diseases of livestock. Working on several major pathogens of cattle and poultry, IAH has an excellent infrastructure for studying diseases in their natural hosts. IAH has recently invested heavily on areas such as transcriptome analysis, proteomics and bioinformatics to underpin the research efforts on studying the complex pathogen-host interactions in important diseases of animals. These recent advances have generated a growing requirement within the IAH to get to grips with cell biology, particularly methods allowing the cellular localization of host and pathogen proteins to be determined with precision, using recent advances in Bioimaging techniques.Image analysis by fluorescence microscopy is becoming a powerful tool for visualising the dynamics of intracellular networks and molecular host-pathogen interactions during infection by pathogens. The current proposal is to obtain funds to purchase a new confocal microscope for the Compton Laboratory to undertake research projects in different groups working on various pathogens. Some of the examples of research projects that would benefit from the confocal microscope are (a) Marek's disease in chickens to examine the complex interactions of MDV and host in cell-to-cell spread and the unique ability of the feather follicel epithelium to support cell-free virus production (b) Analysis of the repertoire and function of bacterial Type III secreted effector proteins (c) Host cell invasion of Eimeria tenella (d) dynamics of cell types and interactions in mycobacterial granuloma in cattle (e) Coronavirus-host proteins (f) biology of avian dendritic cells and (g) examining the role of chicken toll-like receptors. Availability of the confocal microscope with facilities for live cell imaging is vital for the success of many of these projects and for the fundamental understanding of the molecular interactions of several pathogens with their natural hosts