Core C - Proteomics Core

核心 C - 蛋白质组学核心

• 批准号: 10153659
• 负责人: Jeffrey R Johnson
• 金额: $ 30万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153659
• 关键词: Biological Assay; Cells; Clinical; Collaborations; Data; Data Analyses; Dengue; Dengue Infection; Dengue Virus; Disease; Genes; Genomics; Global Change; Human; Immune; Immune response; Immunologic Monitoring; Immunology; Individual; Label; Laboratories; Mass Spectrum Analysis; Measures; Monitor; Outcome; Pathway interactions; Patients; Pattern; Peptides; Phosphorylation; Population; Post-Translational Protein Processing; Proteins; Proteomics; Protocols documentation; Reaction; Resolution; Sampling; System; Ubiquitination; Vaccination; Virus Diseases; base; clinically relevant; cohort; data modeling; detection assay; genomic data; interest; novel; protein complex; response; synthetic peptide; validation studies

SUMMARY In the Proteomics Core (Core C), part of the Dengue Human Immunology Project Consortium, we will apply mass spectrometry-based proteomics approaches to quantitatively measure responses to viral infection and vaccination in clinical cohorts. We will first measure global changes in a number of protein readouts including phosphorylation, ubiquitination, and protein abundance, in ex vivo primary cells infected with Dengue virus to identify proteins of interest worth pursuing in more targeted proteomics studies in clinical samples. Data from Core C will be integrated with data from Cores B (Genomics Core) and D (Immune Monitoring Core) by Core E (Data Analysis and Modeling Core) to select approximately 200 proteins for which to develop sensitive assays for detection and quantification from very limited sample amounts. Finally, we will apply the developed assays to quantify protein responses in patient-derived samples from clinical cohorts in natural populations to compare clinical outcomes of viral infection and vaccination. These targeted proteomics approach will also be used to conduct ex vivo validation studies after perturbing predicted host driver genes.

概括 在作为登革热人类免疫学项目联盟一部分的蛋白质组学核心（核心 C）中，我们将申请 基于质谱的蛋白质组学方法可定量测量对病毒感染的反应和 临床队列中的疫苗接种。我们将首先测量一些蛋白质读数的全局变化，包括 感染登革热病毒的离体原代细胞的磷酸化、泛素化和蛋白质丰度 识别值得在临床样本中更有针对性的蛋白质组学研究中追求的感兴趣的蛋白质。数据来自 Core C 将通过 Core E 与 Core B（基因组学核心）和 D（免疫监测核心）的数据集成 （数据分析和建模核心）选择大约 200 种蛋白质来开发敏感检测 用于从非常有限的样品量中进行检测和定量。最后，我们将应用开发的检测方法 量化自然人群临床队列中患者来源样本中的蛋白质反应，以进行比较 病毒感染和疫苗接种的临床结果。这些有针对性的蛋白质组学方法也将用于 在干扰预测的宿主驱动基因后进行离体验证研究。