Deciphering ubiquitin-regulated host responses to the intracellular pathogen Legi

破译泛素调节的宿主对细胞内病原体 Legi 的反应

基本信息

批准号：
8415836
负责人：
Craig R. Roy
金额：
$ 20.79万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8415836
关键词：
Animal Model Bacteria Bacterial Typing Binding Biochemical Biogenesis Biological Breathing Cell Proliferation Cell physiology Cell surface Cells Cellular Stress Response Computer Simulation Cues Cytosol Data Detection Disease Outbreaks Engineering Enzymes Evolution Fresh Water Genetic Transcription Goals Homeostasis Human Immune Immune response Immune system Immunologic Surveillance Infection Inflammatory Invaded Knowledge Legionella Legionella pneumophila Legionnaires&apos Disease Lipids Maps Methodology Microbe Modification Molecular Molecular Profiling Monitor Outcome Pathway interactions Process Proteins Proteomics Protozoa Regulation Sensory Signal Transduction Site Source Staging Stimulus Stress Response Signaling Swimming Systems Biology Translations Type IV Secretion System Pathway Ubiquitin Ubiquitination Vacuole Virulent Water aerosolized antimicrobial base combat cytokine design human FRAP1 protein in vivo interest macrophage mutant novel pathogen pathogenic bacteria respiratory response surveillance network trafficking ubiquitin ligase

项目摘要

DESCRIPTION (provided by applicant): Distinguishing pathogenic from non-pathogenic microbes presents an interesting challenge to the host immune system and is critical for eliciting the appropriate immune response to combat the invading pathogen. Vacuolar pathogens have evolved multiple strategies to manipulate host functions to promote intracellular survival, necessitating co-evolution of immune molecular sensory networks that detect the pathogen attempts at subversion. To dissect how this process occurs at the molecular level we have developed methodology that monitors modifications on host proteins to reverse-engineer the host response networks to pathogenic infection in silico. To this end, we are using the respiratory pathogen Legionella pneumophila as a model organism to decipher specific regulation of host cellular pathways to pathogenic challenge. The overall goal of the project is to use biochemical and molecular approaches to characterize how cellular pathways in macrophages utilize regulatory molecular modifications, such as ubiquitin, to specifically alter the outcome of signaling cascades in response pathogenic infection. Specific emphasis is placed on the cellular cascades that coordinate the cytokine response of innate immune cells.

描述（由申请人提供）：区分致病性和非致病性微生物对宿主免疫系统提出了有趣的挑战，并且对于引发适当的免疫反应以对抗入侵的病原体至关重要。液泡病原体已经进化出多种策略来操纵宿主功能以促进细胞内存活，因此需要免疫分子感觉网络的共同进化来检测病原体的颠覆企图。为了剖析这个过程如何在分子水平上发生，我们开发了监测宿主蛋白质修饰的方法，以在计算机上对宿主对病原体感染的反应网络进行逆向工程。为此，我们使用呼吸道病原体嗜肺军团菌作为模式生物来破译宿主细胞途径对病原体攻击的具体调节。该项目的总体目标是利用生化和分子方法来表征巨噬细胞中的细胞通路如何利用调节性分子修饰（例如泛素）来特异性改变信号级联反应响应病原体感染的结果。特别强调协调先天免疫细胞的细胞因子反应的细胞级联。