Immunomics Research Core

免疫组学研究核心

• 批准号: 10551705
• 负责人: Monica Cappelletti
• 金额: $ 40.79万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10551705
• 关键词: Anti-Infective Agents; Antibiotics; Area; Bioinformatics; Biological Assay; Blood; Candida; Candida albicans; Cell Culture Techniques; Cells; Chromatin; Consensus Sequence; DNA; DNA Methylation; DNA-Protein Interaction; Data; Data Analyses; Data Set; Development; Disease model; Enhancers; Ensure; Epigenetic Process; Gene Expression Profile; Generations; Genetic; Genome; Genotype; Goals; Grant; Hospitals; Immune; Immune response; Immunoassay; Immunophenotyping; In Vitro; Infection; Innate Immune Response; Leadership; Libraries; Life; Macrophage; Measures; Methicillin Resistance; Microbe; Outcome; Patient-Focused Outcomes; Patients; Performance; Phenotype; Plasma; Preparation; Protocols documentation; Publishing; Reagent; Research; Research Project Grants; Research Support; Role; Running; Sampling; Sepsis; Services; Shapes; Standardization; Staphylococcus aureus; System; Technical Expertise; Techniques; Technology; Testing; adaptive immune response; bisulfite sequencing; candidemia; cell type; cost; data exchange; data management; design; epigenome; epigenomics; experimental study; immune function; immunological diversity; innovation; interest; methicillin resistant Staphylococcus aureus; mouse model; next generation sequencing; programs; resistant strain; transcriptome; transcriptome sequencing; transcriptomics; whole genome

IMMUNOMICS AND EPIGENOMICS CORE PROJECT SUMMARY/ABSTRACT The Immunomics and Epigenomics Core (IEC) is an essential component of the overall program that will centralize the execution of a number of assays that will enable the characterization of immune responses. The overall proposal aims to understand epigenetic changes in patients infected by methicillin-resistant Staphylococcus aureus (MRSA) or Candida albicans Candidemia (CAC) and the immunologic functions shaping antibiotic-persistent from resolving outcomes. The IEC Core will provide skilled technical and scientific expertise to enable the PIs to achieve their research goals by carrying out the following assays. We will characterize the genetics and epigenetics of MRSA and CAC isolated from patient samples from long reads. Using PacBio circular consensus sequences we will reconstruct the genomes of SA and Candida isolated derived from patient samples, derive genomes and epigenomes of these microbes and related the data to patient outcomes. We will profile transcriptomes and epigenomes from short read data. This will include the generation of whole genome bisulfite sequencing libraries in order to characterize the cell types and their abundance in blood and plasma DNA samples. Chromatin accessibility will be profiled using ATC-seq. Protein-DNA interaction will also be profiled using CUT&Run protocols. Finally, we will also characterize innate and adaptive immune responses in CAC and MRSA patient samples and the phenotype and function of PAMP-stimulated macrophages. The Core has validated standardized cell cultures, immunophenotyping panels, multiplex Luminex, ultrasensitive Simoa assay to support the research of the Projects. We will be responsible for performing these assays, interpreting the data and working with the Bioinformatic and Data Management (BDM) Core to transfer the data and the Computational (CPM) Core for further analysis.

免疫组学和表观基因组学核心 项目概要/摘要 免疫组学和表观基因组学核心 (IEC) 是整个计划的重要组成部分，它将 集中执行许多分析，从而能够表征免疫反应。这 总体提案旨在了解耐甲氧西林感染患者的表观遗传变化 金黄色葡萄球菌 (MRSA) 或白色念珠菌 念珠菌血症 (CAC) 与免疫功能塑造 抗生素持久性从解决结果。 IEC 核心将提供熟练的技术和科学专业知识 使 PI 能够通过进行以下分析来实现其研究目标。我们将表征 从长读数的患者样本中分离出 MRSA 和 CAC 的遗传学和表观遗传学。使用 PacBio 我们将重建从患者身上分离出的 SA 和念珠菌的基因组的圆形共有序列 样本，得出这些微生物的基因组和表观基因组，并将数据与患者结果相关联。我们将 从短读数据中分析转录组和表观基因组。这将包括全基因组的生成 亚硫酸氢盐测序文库，用于表征细胞类型及其在血液和血浆中的丰度 DNA 样本。将使用 ATC-seq 分析染色质可及性。蛋白质-DNA相互作用也将 使用 CUT&Run 协议进行分析。最后，我们还将描述先天性和适应性免疫反应的特征 CAC 和 MRSA 患者样本以及 PAMP 刺激的巨噬细胞的表型和功能。核心 已验证标准化细胞培养物、免疫表型分析板、多重 Luminex、超灵敏 Simoa 分析来支持项目的研究。我们将负责执行这些检测、解释 数据并与生物信息学和数据管理 (BDM) 核心一起传输数据和 用于进一步分析的计算 (CPM) 核心。