Immune Responses to Malaria, HIV and SARS-CoV-2 Infection and Immunization - Service Core

对疟疾、HIV 和 SARS-CoV-2 感染的免疫反应和免疫接种 - 服务核心

• 批准号: 10631094
• 负责人: Peter Skene
• 金额: $ 81.56万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-19 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631094
• 关键词: 2019-nCoV; ACE2; Antibodies; Antibody Specificity; Antigens; Avidity; B-Lymphocytes; B-cell receptor repertoire sequencing; Biological; Biological Assay; Cell Separation; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Characteristics; Cross-Sectional Studies; Cytometry; Deposition; Environment; Evaluation; Flow Cytometry; Gene Expression; Generations; HIV; HIV-1; Human; Immune; Immune response; Immune system; Immunity; Immunization; Label; Libraries; Malaria; Methods; Modality; Molecular; Myelogenous; Peptide/MHC Complex; Peptides; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Population; Protein Analysis; Proteomics; Research; Research Project Grants; Resources; Role; SARS-CoV-2 infection; Sampling; Serology; Serology test; Services; Sorting; Specificity; Stains; Standardization; System; T cell receptor repertoire sequencing; T-Cell Receptor; Whole Blood; antigen-specific T cells; biological research; cell type; cost efficient; cytokine; data ingestion; data integration; data visualization; epigenomics; genomic platform; innovation; longitudinal analysis; multiple omics; pathogen; protein biomarkers; protein expression; receptor; response; single cell sequencing; single-cell RNA sequencing; transcriptomics

Abstract The immune system is composed of many heterogeneous cell types that respond in a synergistic manner to mount both immediate and long-lived immunity against pathogens. The complexity of the immune system necessitates an integrated view of multiple biological modalities to understand different roles of varying cell types of the immune system. Detailed transcriptomic and protein analysis at the single cell level is essential to follow the immune system’s response to pathogens in mounting an antigen specific response. With heavy emphasis on assays that facilitate the analysis of antigen-specific cellular and humoral immune responses, the Integrative Multi-Omics Core will serve as a resource to standardize, optimize, and perform multi-omic single cell research to support the biological research objectives of Projects 1, 2 and 3. The implementation of highly standardized and automated assays will enable longitudinal and cross-sectional analysis of the human samples within and across the research projects. Specifically, the core will provide: i. standardized high throughput flow cytometry, bulk transcriptomics and plasma proteomics; ii. well established synergistic assays for the analysis of antigen-specific T cell and B cell responses, including several orthogonal approaches for profiling antigen-specific T cells and a range of systems serology assays; and iii. optimized cost-efficient single-cell sequencing multi-omics methods for analysis of cellular protein-expression, gene-expression, adaptive receptor sequences, antigen-specificity, and epigenomics based on the 10x Genomics platform. Furthermore, we will use a collaborative cloud environment to support data ingest, processing and provision to the DMAC for deposition into ImmPort in support of rapid public access and innovation in data integration and visualization.

摘要 免疫系统由许多异质细胞类型组成，它们以协同方式应答。 这是建立针对病原体的即时和长期免疫力的方式。的复杂性 免疫系统需要对多种生物形态进行综合观察， 免疫系统中不同类型细胞的不同作用。详细的转录组学和蛋白质 单细胞水平的分析对于跟踪免疫系统对病原体的反应至关重要 产生抗原特异性反应。着重强调了促进 分析抗原特异性细胞和体液免疫反应，整合多组学 核心将作为一个资源，标准化，优化和执行多组学单细胞研究 支持项目1、2和3的生物学研究目标。实施高度 标准化和自动化的分析将使纵向和横截面分析的 研究项目内部和之间的人类样本。具体而言，核心将提供： 标准化高通量流式细胞术、批量转录组学和血浆蛋白质组学; ii.以及 建立了用于分析抗原特异性T细胞和B细胞应答的协同测定， 包括几种用于分析抗原特异性T细胞的正交方法和一系列 系统血清学测定;和iii.优化的成本效益单细胞测序多组学 分析细胞蛋白质表达、基因表达、适应性受体的方法 基于10 x Genomics平台的序列、抗原特异性和表观基因组学。 此外，我们将使用协作云环境来支持数据获取、处理 并向DMAC提供沉积到ImmPort的资金，以支持公众快速访问， 数据集成和可视化方面的创新。