HIPC U19 Project 1

重债穷国 U19 项目 1

• 批准号: 10420948
• 负责人: Matthew C. Altman
• 金额: $ 32.63万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-29 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10420948
• 关键词: Acute; Adult; Allergens; Allergic; Antibodies; Antigens; Asthma; B-Cell Antigen Receptor; B-cell receptor repertoire sequencing; Blood specimen; CD8-Positive T-Lymphocytes; Cells; Child; Childhood; Chronic Disease; Clinical; Cytometry; DNA Methylation; Data; Data Analyses; Disease; Frequencies; Future; Gene Expression; Generations; Genetic; Genomics; Genotype; Goals; Hypersensitivity; IgE; Immune; Immune response; Immunity; Immunologic Memory; Immunology; Immunophenotyping; Infection; Inflammatory; Intervention Studies; Kinetics; Lead; Ligands; Link; Lymphocyte; Measures; Membrane Proteins; Methods; Molecular; Morbidity - disease rate; Mucous Membrane; Nasal turbinate bone structure; Nature; Nose; Obesity; Outcome; Pathogenesis; Pathway interactions; Pattern; Phenotype; Population; Populations at Risk; Proteome; Receptor Cell; Reporting; Research; Resolution; Sampling; Severities; Severity of illness; Source; Sputum; Standardization; Swab; Symptoms; System; Systems Biology; T-Lymphocyte; Time; Training; Viral; Viral Respiratory Tract Infection; Virus; Vulnerable Populations; acute infection; adaptive immune response; airway immune response; atopy; chronic respiratory disease; clinical phenotype; comorbidity; demographics; disorder prevention; experience; high dimensionality; human disease; insight; molecular phenotype; mortality; multiple omics; novel; peripheral blood; programs; proteogenomics; pulmonary function; respiratory; respiratory infection virus; respiratory virus; response; sample collection; spatiotemporal; transcriptome

PROJECT SUMMARY/ABSTRACT – PROJECT 1 Acute respiratory viral infections (ARVI) are the most frequently occurring global illness producing significant morbidity and mortality, particularly in vulnerable populations. Children suffer higher frequencies of ARVI than adults and often experience re-infections. Common chronic diseases of childhood, most notably asthma but also allergies (atopy) and obesity, can predispose to increased severity of ARVI. The goal of Project 1 is to understand the longitudinal airway and systemic, innate and adaptive, immune responses to ARVI in vulnerable groups of children with asthma, atopy, and obesity compared to control children without these comorbidities. Furthermore, we will link these responses to clinical outcomes including infection duration and severity. Project 1 is highly synergistic with Project 2 and the Overall program by utilizing similar sample types, timing of sample collection, and common clinical endpoints; it differs by studying a distinct population of at-risk children and it includes disease specific assessments of allergic immune responses. Project 1 benefits from the overall program’s shared multi-omics approaches through a Genomics Core for the sample processing and generation of airway host transcriptome, proteome, DNA methylation, and viral quantity and expression data, along with host genetics. Similarly, it shares the Adaptive Phenotyping Core for the generation of high dimensional cytometry data to broadly characterize immune cell phenotypes and for detailed identification of antigen-specific cells. The first aim will determine differences in longitudinal respiratory innate immune profiles in children with and without asthma, atopy, and obesity in response to ARVI using multi-omic assessments of airway samples. The second aim will determine differences in short-term and long-term adaptive cellular responses including a detailed characterization of viral-specific and allergen-specific T cell populations. The third aim will utilize single cell gene expression, TCR/BCR sequencing, and surface protein quantification (TotalSeq) to provide cell specific granularity of both mucosal and systemic responses. This study will determine networks of airway and systemic immune pathways that lead to adaptive and maladaptive responses to ARVI in vulnerable children. Our research program will produce novel mechanistic insights into the diversity and commonality of immune responses to ARVI and use cutting-edge methods to provide novel insights for future studies of disease prevention and treatment.

项目总结/摘要-项目1 急性呼吸道病毒感染（阿尔维）是最常见的全球性疾病， 发病率和死亡率，特别是在弱势群体中。儿童患阿尔维的频率高于 成年人，经常经历再次感染。儿童常见的慢性疾病，最明显的是哮喘， 过敏（特应性）和肥胖也可使阿尔维的严重程度增加。项目1的目标是 了解纵向气道和全身，先天性和适应性，免疫反应，阿尔维， 与对照组儿童相比，哮喘、特应性和肥胖的易感儿童群体 合并症。此外，我们将这些反应与临床结果联系起来，包括感染持续时间和 严重性。项目1与项目2和总体方案通过利用类似的样品类型高度协同， 样本采集的时间和常见的临床终点;通过研究不同的高危人群， 它包括过敏性免疫反应的疾病特异性评估。项目1受益于 整个计划的共享多组学方法，通过基因组学核心进行样本处理， 产生气道宿主转录组、蛋白质组、DNA甲基化以及病毒数量和表达数据， 沿着宿主遗传学。同样，它共享用于产生高表达的适应性表型核心。 三维细胞计数数据，以广泛表征免疫细胞表型，并详细鉴定 抗原特异性细胞。第一个目标是确定纵向呼吸先天免疫谱的差异 在患有和不患有哮喘、特应性和肥胖的儿童中，使用多组学评估对阿尔维的反应， 气道样本第二个目标将确定短期和长期适应性细胞的差异， 包括病毒特异性和过敏原特异性T细胞群体的详细表征。的 第三个目标将利用单细胞基因表达、TCR/BCR测序和表面蛋白定量 （TotalSeq）来提供粘膜和全身应答两者的细胞特异性粒度。本研究将 确定导致适应性和适应不良的气道和全身免疫途径的网络 在脆弱儿童中对阿尔维抗逆转录病毒疫苗的反应。我们的研究计划将产生新的机械见解， 对阿尔维免疫反应的多样性和共同性，并使用尖端方法提供新的 对未来疾病预防和治疗研究的见解。