Center for Structural Biology of HIV RNA

HIV RNA结构生物学中心

• 批准号: 10505786
• 负责人: ALICE TELESNITSKY
• 金额: $ 554.93万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-09 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10505786
• 关键词: Address; Area; Biological; Biological Process; Biology; Cells; Chemistry; Complex; Cryoelectron Microscopy; Crystallization; Crystallography; Development; Disease; Electron Microscopy; Elements; Environment; Face; Gene Expression; Genetic Transcription; Goals; HIV; HIV-1; Host Defense; Image; Immune response; Immunologist; Infection; Integration Host Factors; Maintenance; Microscopy; Molecular; Optics; Play; Preparation; Prevention; Prevention approach; Process; Property; Proteins; Proviruses; RNA; RNA Splicing; RNA chemical synthesis; RNA metabolism; RNA-Protein Interaction; RNA-targeting therapy; Research Personnel; Resolution; Role; Sampling; Science; Services; Specialist; Structural Biologist; Structure; Technology; Therapeutic; Therapeutic Uses; Training; Translations; Viral; Viral Proteins; Virion; Virus Replication; base; biophysical techniques; clinically relevant; comparative; disorder prevention; drug discovery; genomic RNA; innovation; light microscopy; member; multidisciplinary; next generation; novel therapeutic intervention; particle; protein complex; protein function; reactivation from latency; structural biology; technology development; technology validation; therapeutic target; trafficking

This application for the Center for Structural Biology of HIV RNA (CRNA) focuses on determining the structural and mechanistic bases of HIV-1 RNA-related replication functions and the host’s response at the cellular, viral, and atomic levels. Although considerable progress has been made over the past 40 years in understanding how proteins function in HIV-1 replication, comparatively little is known about how HIV-1 RNA structures, dynamics, trafficking, and interactions with proteins alternately enable or limit virus replication. The past decade has provided transformative examples of the therapeutic use of RNA and RNA-targeted therapies, and recent progress by members of the proposed team has begun to unlock structural and dynamic features of RNA elements in HIV-1. Because HIV-1 RNA is exceptionally rich in biologic functions, the potential for RNA-targeted approaches in the prevention, maintenance, and cure of HIV-1 disease is highly compelling. However, this potential is limited by the general paucity of high-resolution structural information for RNA and protein-RNA complexes, which reflects inherent challenges in using RNA as a subject for structural analysis and the inadequacy of traditional biophysical approaches to address these challenges. The CRNA will face these challenges for HIV-1 RNA with its multidisciplinary team of structural biologists, chemists, cell and computational biologists, biochemists, immunologists, and virologists. Many are leaders in the study of HIV-1 RNA and the roles of its structures in virus replication, while others are new to the HIV-1 field and bring a fresh perspective and complementary expertise. Together, this team brings cutting edge technologies and incisive biologic approaches to overcome current technological obstacles, enabling mechanistic determination of the role of HIV- 1 RNA structures and associated proteins in viral transcription, splicing, translation, packaging, particle assembly, and interactions with host factors. These studies will enable the CRNA to advance goals of clinical relevance, including the development new RNA-centered strategies for treating HIV-1, the reactivation of latent proviruses as a potential approach for eradicating HIV-1 infection, and the augmentation of host defenses against HIV-1 infection. The proposed studies will also result in the development of powerful new computational, imaging, and structural biology technologies that can be applied to all areas of RNA biology.

此应用于HIV RNA（CRNA）结构生物学中心的应用侧重于确定结构 HIV-1 RNA相关复制函数的机械碱基以及宿主在细胞病毒中的反应 和原子水平。尽管过去40年来取得了相当大的进步，以理解如何 蛋白质在HIV-1复制中的功能，对HIV-1 RNA结构，动力学，动力学，相对较少了解 运输，以及与蛋白质的相互作用，或者可以促进或限制病毒复制。过去十年有 提供了RNA和靶向RNA靶向疗法的治疗用途的变革示例，以及最近 拟议团队成员的进步已开始解锁RNA的结构和动态特征 HIV-1中的元素。因为HIV-1 RNA异常富含生物学功能，因此靶向RNA的潜力 HIV-1疾病的预防，维护和治疗方面的方法具有很高的吸引力。但是，这个 电势受到RNA和蛋白质RNA的高分辨率结构信息的一般缺乏的限制 复合物，反映了将RNA用作结构分析的主题的继承挑战和 传统的生物物理方法不足以应对这些挑战。 CRNA将面对这些 HIV-1 RNA的挑战与其结构生物学家，化学家，细胞和计算的多学科团队 生物学家，生物化学家，免疫学家和病毒学家。许多是HIV-1 RNA研究的领导者和 其结构在病毒复制中的作用，而其他结构是HIV-1领域的新手，并带来了新的视角 和补充专业知识。该团队一起带来了尖端技术和尖锐的生物学 克服当前技术障碍的方法，以确定HIV的作用 1个病毒转录，剪接，翻译，包装，颗粒中的RNA结构和相关蛋白 组装，以及与宿主因素的相互作用。这些研究将使CRNA能够促进临床目标 相关性，包括开发以RNA为中心的治疗HIV-1的策略，潜在的重新激活 证明病毒是消除HIV-1感染的潜在方法，并增加了宿主防御措施 HIV-1感染。拟议的研究还将导致强大的新计算，成像的发展 以及可应用于RNA生物学所有领域的结构生物学技术。