Duke Center for HIV Structural Biology

杜克大学艾滋病毒结构生物学中心

基本信息

批准号：
10643906
负责人：
Priyamvada Acharya
金额：
$ 548.85万
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/10643906
关键词：
Acquired Immunodeficiency Syndrome Adherence Antibodies Autologous B-Cell Activation B-Cell Antigen Receptor B-Cell Receptor Binding B-Lymphocytes Behavior Binding Biology Blocking Antibodies Cell membrane Cells Chronic Disease Clinical Clonal Expansion Complex Development Disease Disease remission Economic Burden Elements Epitopes Evolution Fab Immunoglobulins Glycoproteins Goals HIV HIV Envelope Protein gp120 HIV Infections HIV-1 HIV/AIDS Immune Immune Evasion Immune response Immune system Immunobiology Immunoglobulin Fragments Immunoglobulin Somatic Hypermutation Individual Infection Kinetics Knowledge Mediating Membrane Methods Molecular Conformation Movement Outcome Pathway interactions Peptides Persons Play Process Proviruses Receptor Activation Receptor Signaling Research Research Personnel Resolution Resources Role Series Signal Pathway Signal Transduction Specificity Structure Surface Techniques Therapeutic Time Vaccination Vaccines Viral Viral reservoir Viremia Virus Visualization antiretroviral therapy atomic interactions career env Glycoproteins global health immune activation innovation insight latent HIV reservoir molecular dynamics multilevel analysis neutralizing antibody new therapeutic target pandemic disease prevent receptor receptor binding resistance mechanism response structural biology temporal measurement therapeutic target training opportunity vaccine development vaccine response vaccine trial viral rebound

项目摘要

Abstract – Overall 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 proposed Duke Center for HIV Structural Biology will provide new insights into the dynamics of HIV-1 entry and fusion with the host membrane, the Env-initiated immune activation of B-cell receptors, and the role of anti-Env antibodies in blocking viral rebound. The Center will pursue structural studies that aim to 1) to develop a complete, time resolved and atomically detailed mechanism of HIV-1 Env fusion; 2) to define BCR complex structures with specificity of autologous (anAb) and broadly neutralizing antibodies (bnAb); and 3) to achieve an atomic level understanding of antibody-mediated control of rebound from latent HIV-1 reservoirs. The ultimate goal of these studies is to advance structural biology techniques and knowledge of HIV-1 Env structure-derived disease mechanisms in HIV-1 infection and rebound. Additionally, through its Developmental Core, the Center will provide resources and training opportunities for early career investigators and trainees who are pursuing careers in the field of HIV-1 structural biology.

摘要 – 总体然而，全球约有 4000 万人感染艾滋病毒/艾滋病；尽管经过四十年的深入研究，HIV-1 仍然无法逃脱免疫系统的攻击。通过其在感染和复制过程中的快速结构演变。结构生物学将为 HIV-1 进入和与宿主融合的动态提供新的见解膜、B 细胞受体的 Env 启动的免疫激活以及抗 Env 抗体在该中心将进行结构性研究，旨在 1) 制定完整的时间。 HIV-1 Env 融合的解析和原子详细机制；2) 定义 BCR 复合体结构自体抗体 (anAb) 和广泛中和抗体 (bnAb) 的特异性；3) 达到原子水平；了解抗体介导的对潜伏 HIV-1 病毒库反弹的控制是这些研究的最终目标。研究旨在推进结构生物学技术和 HIV-1 Env 结构衍生疾病的知识此外，该中心还将通过其发展核心，研究 HIV-1 感染和反弹的机制。为早期职业研究者和正在追求的学员提供资源和培训机会 HIV-1结构生物学领域的职业生涯。