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）：区分致病性与非致病微生物对宿主免疫系统提出了一个有趣的挑战，对于引发适当的免疫反应以打击入侵的病原体至关重要。液泡病原体已经发展了多种策略来操纵宿主功能以促进细胞内存活，因此需要共同进化免疫分子感觉网络，以检测颠覆性病原体的尝试。为了剖析该过程在分子水平上的发生方式，我们开发了方法，可以监视宿主蛋白上的修饰，以将宿主反应网络反向硅酸盐的致病性感染逆转。为此，我们将呼吸病原体肺炎肺癌用作模型生物，以破译宿主细胞途径的特定调节致病性挑战。该项目的总体目标是使用生化和分子方法来表征巨噬细胞中的细胞途径如何利用调节性分子修饰（例如泛素），以专门改变响应致病性感染中信号级联的结果。特定的重点放在协调先天免疫细胞细胞因子反应的细胞级联反应上。