Core 3 - Immunobiology Core

核心 3 - 免疫生物学核心

• 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
• 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

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 全世界约有4000万人感染艾滋病毒/艾滋病;然而，保护性疫苗或功能性疫苗 尽管进行了40年的深入研究，但治愈方法仍然难以捉摸。HIV-1通过其免疫系统逃避免疫系统 在感染和复制过程中的快速结构进化。杜克艾滋病毒结构生物学中心将继续研究 HIV-1包膜蛋白进化的结构研究，以阐明结构-功能机制 用于抗逆转录病毒治疗ART后的病毒进入、B细胞和T细胞激活以及病毒反弹。免疫生物学 核心（核心3）汇集了一个团队的研究人员与广泛的专业知识，在细胞和分子 免疫学提供全面、集中的免疫测定服务，以支持三人的努力 项目和其他核心。免疫生物学核心的总体目标是：1）支持项目1，2， 和3用免疫测定和生物化学方案评估细胞系中的B细胞受体信号传导和敲除- 在小鼠中，2）提供用于测量作为B细胞活化读数的MHCII上的肽呈递的测定， 和3）通过从HIV感染的受试者中进行单个B细胞分选用于恢复来支持项目3， Env特异性抗体的表达。免疫生物学核心包括设施、技术和服务 存放在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）和博士博罗（核心联合主任）在牛津大学，博士的生物分子相互作用实验室。 Alam（核心联合主任），DVHI，Saunders博士的蛋白质生产实验室（DHVI）和DHVI Flow 细胞计数设施。 除了与单个项目的互动外，免疫生物学核心还将直接与 发展核心。核心人员将与学员在工作台上携手合作， 分析，重点是稳健的实验设计，适当的技术和适当的分析， 试验结果根据需要，核心小组将为受训人员举办小组讲习班，重点是 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关键的见解 在B细胞表面膜上的细胞受体相互作用，以及从HIV+ 受试者将能够实现与抑制病毒库有关的结构见解。而且 本核心中开发的方法和试剂将提供给研究界， 应用于基础和应用结构免疫学研究。