HIPC U19 Project 1

重债穷国 U19 项目 1

• 批准号: 10598128
• 负责人: Matthew C. Altman
• 金额: $ 12.54万
• 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/10598128
• 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; Innate Immune Response; 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; Seasons; 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; comparison control; data integration; 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.

项目摘要/摘要 - 项目1 急性呼吸道病毒感染（ARVI）是最常见的全球疾病，产生明显的明显 发病率和死亡率，尤其是在弱势群体中。儿童的Arvi频率高于 成人，经常经历重新感染。童年的常见慢性疾病，最著名的是哮喘，但 同样，过敏症（特应性）和肥胖症可能会增加ARVI的严重程度。项目1的目标是 了解纵向气道以及对Arvi的纵向，天生和适应性的免疫反应 与没有这些的对照儿童相比 合并症。此外，我们将将这些反应与临床结果联系起来，包括感染期限和 严重程度。项目1通过使用类似的示例类型，与项目2和整体程序具有高度协同作用， 样品收集的时间和常见的临床终点；它通过研究处于风险的不同人群而有所不同 儿童，其中包括对过敏免疫反应的特定评估。项目1从 整个计划通过基因组学核心共享多摩学方法，用于样本处理和 气道宿主转录组，蛋白质组，DNA甲基化以及病毒量和表达数据的产生， 以及宿主遗传学。同样，它共享自适应表型核心的核心 维数细胞术数据，以广泛表征免疫球表型，并详细识别 抗原特异性细胞。第一个目的将确定纵向呼吸的先天免疫特征的差异 在患有和没有哮喘，特温和肥胖症的儿童中，对ARVI的响应使用多OMIC评估 气道样品。第二个目标将确定短期和长期自适应细胞的差异 响应包括病毒特异性和过敏原特异性T细胞群的详细表征。这 第三目的将利用单细胞基因表达，TCR/BCR测序和表面蛋白定量 （totalSeq）提供粘膜和全身反应的细胞特异性粒度。这项研究会 确定导致适应性和适应不良的气道网络和全身免疫途径 弱势儿童对Arvi的反应。我们的研究计划将产生新颖的机械见解 免疫反应对ARVI的多样性和共同点，并使用尖端方法提供新颖的方法 对预防疾病和治疗的未来研究的见解。