Recognition and Signaling During Infection in Drosphila

果蝇感染期间的识别和信号传导

基本信息

批准号：
7486235
负责人：
JULES A HOFFMAN
金额：
$ 29.53万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7486235
关键词：
Address Adult Affect Anopheles Genus Antibodies Antibody Formation Applications Grants Bacteria Binding Proteins Biochemical Biochemistry Biological Models Candidate Disease Gene Cell Line Cells Cellular biology Chromosomes Class Code Collaborations Communicable Diseases Communities Complement Consensus Culicidae Data Data Set Depth Development Double-Stranded RNA Drosophila genus Drug or chemical Tissue Distribution Endopeptidases Exhibits Family Gene Expression Gene Silencing Generations Genes Genetic Genetic Models Genome Gram-Positive Bacteria Grant Host Defense Hour Immune Immune Response Genes Immune response Immune system Infection Injection of therapeutic agent Injury Insecta Invaded Invertebrates Ions Laboratories Larva Lead Learning Link Mammals Mediating Methods Microbe Molecular Molecular Genetics Mus Mutagenesis Mutate Mutation Names Natural Immunity Numbers Parasites Pathway interactions Pattern Pattern recognition receptor Peptide Hydrolases Peptides Phagocytosis Phenotype Play Principal Investigator Process Production Protein Family Protein Overexpression Proteins Publishing RNA Interference Recombinant Proteins Recombinants Regulation Reporter Reporter Genes Reporting Research Resistance Resistance to infection Role Signal Pathway Signal Transduction Specificity Staging Structure Suppressor Genes Terminology Testing Time Transgenic Organisms Translating United States National Institutes of Health Vertebrates Work antimicrobial antimicrobial peptide base comparative domain mapping extracellular fighting fly frontier fungus loss of function member microbial microorganism mutant novel peptidoglycan recognition protein programs receptor research study response septic structural biology tetraethylpyrazine thioester

项目摘要

Over the last ten years, the highly efficient anti-microbial response of the fruit fly Drosophila has evolved as one of the most powerful biological models to study innate immunity. A hallmark of this response is the challenge-induced expression of potent anti-microbial peptides that counter invading microorganisms. The identity of these molecules has now been established and two signaling pathways leading to their immune-controlled expression have been identified and worked out in significant detail. The last frontier in our understanding of this pristine host defense is the recognition of infectious microorganisms and the molecular mechanisms that link this recognition to activation of the pathways that ultimately lead to expression of the immune response genes. Several families of proteins have been identified recently which may serve as recognition proteins, namely the PGRPs (Peptidoglycan Recognition Proteins), GNBPs (Gram-Negative Binding Proteins) and some of the Thioester Containing Proteins (TEPs). The Aim of the Project is to combine methods of molecular genetics, biochemistry, structural biology and cell biology to elucidate the precise mechanisms by which these recognition proteins and others which remain to be identified, sense microbial patterns and how this interaction translates into activation of intracellular signaling in immune-responsive cells. This Project is crucially dependent on close interactions-both conceptual and methodological- with our partners working on the same central questions in mosquitoes (the Kafatos Laboratory Project 4) and mammals (the Ezekowitz Laboratory, Project 1). Indeed, some of the proposal Aims can only be addressed in collaboration between our groups and through complementing our respective expertise and facilities.

在过去的十年中，果蝇的高效抗微生物反应已发展成为研究先天免疫的最强大的生物模型之一。这种反应的一个标志是攻击诱导的有效抗微生物肽的表达，以对抗入侵的微生物。这些分子的身份现已确定，导致其免疫控制表达的两条信号通路也已被识别并得到了详细的研究。我们对这种原始宿主防御的理解的最后一个前沿是对传染性微生物的识别，以及将这种识别与最终导致免疫反应基因表达的途径激活联系起来的分子机制。最近已鉴定出几个可用作识别蛋白的蛋白质家族，即 PGRP（肽聚糖识别蛋白）、GNBP（革兰氏阴性结合蛋白）和一些含硫酯蛋白（TEP）。该项目的目的是结合分子遗传学、生物化学、结构生物学和细胞生物学的方法，阐明这些识别蛋白和其他有待鉴定的蛋白感知微生物模式的精确机制，以及这种相互作用如何转化为细胞内激活免疫反应细胞中的信号传导。该项目在很大程度上依赖于与我们的合作伙伴在概念和方法上的密切互动，研究蚊子（Kafatos 实验室项目 4）和哺乳动物（Ezekowitz 实验室，项目 1）的相同核心问题。事实上，提案中的一些目标只能通过我们各小组之间的合作以及通过补充我们各自的专业知识和设施来实现。