Center for Structural Biology of HIV RNA

HIV RNA结构生物学中心

• 批准号: 10641972
• 负责人: ALICE TELESNITSKY
• 金额: $ 543.92万
• 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/10641972
• 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; protein purification; 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.

HIV RNA结构生物学中心（CRNA）的这一应用程序侧重于确定结构 以及HIV-1 RNA相关复制功能和宿主在细胞，病毒， 原子水平。尽管在过去的40年里，人们在理解如何 蛋白质在HIV-1复制中的功能，对HIV-1 RNA的结构，动力学， 运输和与蛋白质的相互作用交替地使能或限制病毒复制。过去十年 提供了RNA和RNA靶向疗法的治疗用途的变革性例子， 该研究小组的成员已经开始解开RNA的结构和动力学特征 HIV-1的分子。由于HIV-1 RNA具有非常丰富的生物学功能，因此RNA靶向治疗的潜力 预防、维持和治愈HIV-1疾病的方法是非常引人注目的。但这 由于普遍缺乏RNA和蛋白质-RNA的高分辨率结构信息， 复合物，这反映了使用RNA作为结构分析对象的固有挑战， 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，其结构生物学家，化学家，细胞和计算 生物学家、生物化学家、免疫学家和病毒学家。许多人是HIV-1 RNA研究的领导者， 它的结构在病毒复制中的作用，而其他人是新的HIV-1领域，并带来了新的观点 和互补的专业知识。这支团队共同带来了尖端的技术和敏锐的生物技术， 克服当前技术障碍的方法，使人们能够机械地确定艾滋病毒的作用， 1病毒转录、剪接、翻译、包装、颗粒中的RNA结构和相关蛋白 组装以及与宿主因子的相互作用。这些研究将使CRNA能够推进临床目标， 相关性，包括开发新的以RNA为中心的治疗HIV-1的策略，重新激活潜伏的 前病毒作为根除HIV-1感染的潜在方法，以及增强宿主对 HIV-1感染。拟议中的研究还将导致强大的新的计算，成像， 以及可以应用于RNA生物学所有领域的结构生物学技术。