Membrane Protein Effectors of Pathogen Interactions With Host

病原体与宿主相互作用的膜蛋白效应子

• 批准号: 10689583
• 负责人: Francesca M Marassi
• 金额: $ 44.23万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689583
• 关键词: Membrane; Protein; Effectors; Pathogen; Interactions; Membrane; Protein; Effectors; Pathogen; Interactions

SUMMARY Membrane protein effectors of pathogen interactions with host. The goal of this project is to develop a framework for understanding the way in which the human host defenses interact with microbial pathogens and age-related stressors. Many pathogens have evolved strategies to evade innate immunity by recruiting complement regulatory factors onto the microbial cell surface. Moreover, the ectopic deposits that form in age- related macular degeneration (AMD) and Alzheimer's disease (AD) are also rich in blood proteins involved in innate immunity. Despite the biomedical importance of these processes, mechanistic knowledge is limited. This research project is designed to address this knowledge gap. We focus on determining the structural basis for two central interactions of human blood proteins involved in immunity, hemostasis and cell adhesion and cell migration: (1) interactions with outer membrane proteins from the bacterial pathogen Yersinia pestis that are important for pathogenesis, and (2) interactions with lipids and biominerals that are relevant to the formation of pathological deposits associated with AMD and AD. Proteins in these highly heterogenous environments play central roles in human health but are highly under-represented in the scientific knowledge base. We aim to bridge this fundamental knowledge gap. Addressing these problems is important for advancing comprehensive knowledge of the disease process and for developing diagnostic, preventive, and therapeutic approaches. The research strategy is multidisciplinary. It relies significantly on structural biology techniques, particularly solution NMR and solid-state NMR. 1

概括 病原体与宿主相互作用的膜蛋白效应子。该项目的目的是开发 了解人类宿主防御与微生物病原体相互作用的框架和 与年龄相关的压力源。许多病原体已经发展了通过招募来逃避先天免疫力的策略 补充调节因子在微生物细胞表面上。此外，以年龄形式形成的异位沉积物 相关的黄斑变性（AMD）和阿尔茨海默氏病（AD）也富含参与的血液蛋白 先天免疫。尽管这些过程具有生物医学的重要性，但机械知识还是有限的。这 研究项目旨在解决这一知识差距。我们专注于确定结构性基础 与免疫，止血和细胞粘附和细胞有关的人血蛋白的两个中心相互作用 迁移：（1）与来自细菌病原体耶尔森氏菌的外膜蛋白相互作用 对发病机理重要，（2）与脂质和生物矿物质的相互作用，与形成有关 与AMD和AD相关的病理沉积物。这些高度异质环境中的蛋白质播放 在人类健康中的核心作用，但在科学知识基础上的代表性不足。我们旨在桥接 这个基本知识差距。解决这些问题对于提高全面很重要 了解疾病过程以及开发诊断，预防和治疗方法。这 研究策略是多学科的。它非常依赖结构生物学技术，尤其是解决方案 NMR和固态NMR。 1