Core 3 - Immunobiology Core

核心 3 - 免疫生物学核心

基本信息

批准号：
10506666
负责人：
Derek Wilson Cain
金额：
$ 123.3万
依托单位：
DUKE UNIVERSITY
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：
2022-06-14 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10506666
关键词：
AIDS/HIV problem Affinity Anatomy Antibodies Antibody Affinity Antigens Autologous B-Cell Activation B-Cell Antigen Receptor B-Lymphocytes Binding Biochemical Biological Assay Cell Line Cell Separation Cell surface Cells Cellular Assay Cellular Immunology Communities Cryopreservation DNA cassette Development Distal Educational process of instructing Educational workshop Evaluation Event Evolution Experimental Designs Flow Cytometry Goals HIV HIV Antibodies HIV-1 Helper-Inducer T-Lymphocyte Histocompatibility Antigens Class II Human Human Resources Immune system Immunoassay Immunobiology Immunologics Immunology In Vitro Individual Infection Institutes Investigation Journals Knock-in Mouse Laboratories Lead Leukapheresis Ligation Light Measurement Measures Membrane Methodology Methods Molecular Immunology Mouse Cell Line Mus Peptides Persons Plasmids Production Proteins Protocols documentation Reagent Receptor Signaling Recovery Reproducibility Research Research Personnel Research Project Grants Resistance Resources Reverse Transcriptase Polymerase Chain Reaction Sampling Services Signal Transduction Structure Structure of germinal center of lymph node T-Cell Activation T-Lymphocyte Techniques Technology Translating Universities Vaccines Viral Viral reservoir Work antiretroviral therapy env Gene Products expectation experimental analysis extracellular vesicles gene product in vitro Assay insight inter-institutional neutralizing antibody novel novel strategies screening structural biology success uptake viral rebound virology

项目摘要

Abstract – Core 3 – Immunobiology Core Approximately 40 million people worldwide are living with HIV/AIDS; however, a protective vaccine or functional cure remain elusive despite four decades of intense research. HIV-1 evades the immune system through its rapid structural evolution during infection and replication. The Duke Center for HIV Structural Biology will pursue structural studies of the evolution of the HIV-1 Envelope (Env) protein to elucidate structure-function mechanisms for viral entry, B-cell and T-cell activation, and viral rebound after antiretroviral therapy ART. The Immunobiology Core (Core 3) brings together a team of investigators with extensive expertise in cellular and molecular immunology to provide comprehensive, centralized immunoassay services to support the efforts of the three projects and the other cores. The overall objectives of the Immunobiology Core are to 1) support Projects 1, 2, and 3 with immunoassays and biochemical protocols to evaluate B cell receptor signaling in cell lines and knock- in mice, 2) provide assays for measurements of peptide presentation on MHCII as a read-out of B cell activation, and 3) support Project 3 by performing single B cell sorting from HIV-infected subjects for recovery and expression of Env-specific antibodies. The Immunobiology Core comprises facilities, technologies, and services housed in the cellular immunology laboratories of Dr. Cain (Core Lead) at the Duke Human Vaccine Institute (DHVI) and Dr. Borrow (Core Co-director) at Oxford University, the biomolecular interaction laboratory of Dr. Alam (Core Co-director) at DVHI, the protein production laboratory of Dr. Saunders (DHVI), and the DHVI Flow Cytometry Facility. In addition to interactions with individual projects, the Immunobiology Core will also directly interface with the Developmental Core. Core personnel will work hand-in-hand with trainees at the bench for the teaching of assays, with emphasis on robust experimental design, proper technique, and appropriate analysis of experimental results. As needed, the Core will host small-group workshops for trainees that focus on immunological topics or methodologies related to Core activities. The assays and services provided by the Immunobiology Core are critical to the success of the research projects. The provision of immunoassays will provide key insights into the propagation of signals induced by antigen-B cell receptor interactions at the B cell surface membrane, and the isolation of novel Env antibodies from HIV+ subjects will enable structural insights pertaining to suppression of the viral reservoir. Moreover, the methodologies and reagents developed in this Core will be made available to the research community for application in basic and applied structural immunology research.

摘要 – 核心 3 – 免疫生物学核心全世界大约有 4000 万人感染了艾滋病毒/艾滋病，但是，保护性疫苗或功能性药物；尽管经过四十年的深入研究，HIV-1 通过其免疫系统逃避，但治愈方法仍然难以实现。杜克大学艾滋病病毒结构生物学中心将致力于研究感染和复制过程中的快速结构进化。 HIV-1 包膜 (Env) 蛋白进化的结构研究，以阐明结构功能机制抗逆转录病毒疗法 ART 后的病毒进入、B 细胞和 T 细胞激活以及病毒反弹。核心（核心 3）汇集了在细胞和分子领域拥有丰富专业知识的研究人员团队免疫学提供全面、集中的免疫检测服务，支持三者的努力免疫生物学核心的总体目标是 1) 支持项目 1、2、 3 使用免疫测定和生化方案来评估细胞敲除系中的 B 细胞受体信号传导 - 在小鼠中，2) 测定可测量 MHCII 上的肽呈递，作为 B 细胞激活的读数， 3) 支持项目 3，对 HIV 感染者进行单 B 细胞分选以促进康复和免疫生物学核心包括设施、技术和服务。位于杜克人类疫苗研究所 Cain 博士（核心负责人）的细胞免疫学实验室（DHVI）和牛津大学的 Borrow 博士（联合主任），Dr. Borrow 的生物分子相互作用实验室。 Alam（联合主任），DVHI、Saunders 博士的蛋白质生产实验室 (DHVI) 和 DHVI Flow 细胞计数设施。除了与各个项目的交互之外，免疫生物学核心还将直接与发展核心人员将与实习生携手合作，进行教学。分析，重点是稳健的实验设计、正确的技术和适当的分析根据需要，核心将为学员举办小组研讨会，重点关注实验结果。与核心活动相关的免疫学主题或方法。免疫生物学核心提供的检测和服务对于研究项目的成功至关重要。免疫测定的提供将为抗原 B 诱导的信号传播提供重要见解 B 细胞表面膜上的细胞受体相互作用，以及从 HIV+ 中分离新型 Env 抗体受试者将能够获得有关抑制病毒库的结构见解。本核心开发的方法和试剂将提供给研究界在基础和应用结构免疫学研究中的应用。