Project 2

项目2

基本信息

批准号：
10435216
负责人：
Maria Virginia Pascual
金额：
$ 68.17万
依托单位：
RESEARCH INST NATIONWIDE CHILDREN'S HOSP
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2022-12-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10435216
关键词：
2019-nCoV ATAC-seq Adult Affect Antibody Response Antibody titer measurement B-Lymphocytes Bacterial Infections Biological Assay Blood Blood Cells CD8-Positive T-Lymphocytes COVID-19 vaccine Cell Count Cell Nucleus Cell Volumes Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Child Childhood Chromatin Custom Data Data Set Development Disease Enrollment Epigenetic Process Exposure to Gene Expression Profile Genetic Transcription Health Human Immune Immune response Immune system Immunity Immunologic Monitoring Immunophenotyping Infant Infection Influenza Influenza vaccination Knowledge Learning Life Longevity Longitudinal Studies Molecular Monitor Outcome Participant Pathway interactions Pattern recognition receptor Peripheral Blood Mononuclear Cell Phenotype Population Production Property Risk SARS-CoV-2 infection Sample Size Sampling Shapes Systems Biology Technology Vaccination Vaccines Viral Viral Respiratory Tract Infection Virus Virus Diseases age group age related analysis pipeline commensal microbes cytokine epigenome experience flexibility genome-wide high risk immune function imprint influenza infection innovative technologies multidimensional data pathogenic microbe respiratory virus response seasonal influenza severe COVID-19 tool transcriptome transcriptome sequencing trend

项目摘要

ABSTRACT Infants and young children are at higher risk for severe manifestations of certain respiratory viruses, such as influenza and RSV, compared to older children or adults. Interestingly, SARS-CoV-2 infection has shown the opposite trend, with infants being at lower risk of serious outcomes. The molecular and cellular mechanisms underpinning vulnerability to some infections and protection from others are poorly understood, but intrinsic properties of the post-natal immune system might be at their core. Systems biology tools can resolve these knowledge gaps through detailed analysis of the transcriptome, epigenome and function of immune cell populations across the life span. This project capitalizes on our experience in studying the human immune system through childhood in health and disease, and the availability of immune monitoring assays for use with small-volume samples. Recently, we have leveraged innovative technologies, i.e., ATAC-seq for assessing chromatin accessibility, RNA-seq, high-definition cellular immunophenotyping at the bulk and single cell levels as well as custom-built integrative analysis pipelines. Our preliminary data confirm that we can maximally leverage infant samples to capture transcriptional and regulatory genome-wide signatures associated with the developing immune system in response to viral infections and vaccination with unprecedented granularity. We propose to assess the immune responses to infection with two viruses, influenza and SARS-CoV-2, occurring in the first six months of life by leveraging our immune profiling platform. We will track age-related changes in immune cell composition, transcriptome and epigenome during this first encounter with the virus and will subsequently monitor these parameters upon vaccination against these viruses yearly for a period of three years. Aim 1 will define the phenotype/cell composition, transcriptome and epigenome of infant PBMCs upon their first encounter with either Influenza or SARS-CoV-2 viruses. Aim 2 will Characterize the PBMC phenotype/cell composition, transcriptome and epigenome in response to vaccination against influenza and SARS-CoV-2.

抽象的婴儿和幼儿出现某些呼吸道病毒严重症状的风险较高，例如与年龄较大的儿童或成人相比，流感和RSV。有趣的是，SARS-CoV-2 感染表明相反的趋势，婴儿发生严重后果的风险较低。分子和细胞机制人们对某些感染的脆弱性和对其他感染的保护的认识知之甚少，但本质上产后免疫系统的特性可能是其核心。系统生物学工具可以解决这些问题通过详细分析免疫细胞的转录组、表观基因组和功能来弥补知识差距整个生命周期的人口。该项目利用了我们研究人体免疫的经验整个童年时期的健康和疾病系统，以及免疫监测分析的可用性小体积样品。最近，我们利用创新技术，即 ATAC-seq 来评估染色质可及性、RNA-seq、批量和单细胞水平的高清细胞免疫表型分析以及定制的综合分析管道。我们的初步数据证实我们可以最大程度地利用婴儿样本来捕获与婴儿相关的转录和调控全基因组特征以前所未有的粒度开发免疫系统以应对病毒感染和疫苗接种。我们建议评估对流感和 SARS-CoV-2 两种病毒感染的免疫反应，通过利用我们的免疫分析平台，在生命的前六个月内发生。我们将跟踪与年龄相关的在第一次接触病毒期间，免疫细胞组成、转录组和表观基因组发生变化随后将在每年接种这些病毒疫苗后监测这些参数，持续一段时间三年。目标 1 将定义婴儿 PBMC 的表型/细胞组成、转录组和表观基因组当他们第一次接触流感或 SARS-CoV-2 病毒时。目标 2 将表征 PBMC 表型/细胞组成、转录组和表观基因组对流感疫苗的反应 SARS-CoV-2。