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.

总结 在蛋白质组学核心（核心C），登革热人类免疫学项目联盟的一部分，我们将申请 基于质谱的蛋白质组学方法定量测量对病毒感染的反应， 在临床队列中接种疫苗。我们将首先测量一些蛋白质读数的全球变化，包括 在用登革病毒感染的离体原代细胞中， 在临床样品中鉴定值得在更有针对性的蛋白质组学研究中追求的感兴趣的蛋白质。数据从 核心C将通过核心E与核心B（基因组学核心）和D（免疫监测核心）的数据整合 (Data分析和建模核心），以选择大约200种蛋白质，用于开发敏感的检测方法 用于从非常有限的样品量进行检测和定量。最后，我们将应用开发的检测方法 定量来自自然人群临床队列的患者来源样本中的蛋白质应答， 病毒感染和疫苗接种的临床结果。这些靶向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。