The Center for HIV RNA Studies (CRNA)

HIV RNA 研究中心 (CRNA)

• 批准号: 9132308
• 负责人: MARCO SALEMI
• 金额: $ 16.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9132308
• 关键词: Acquired Immunodeficiency Syndrome; Antiviral Agents; Area; Biological Process; Biology; Cells; Complex; Development; Electrons; Genetic Transcription; Goals; HIV; HIV Infections; HIV-1; Host Defense; In Vitro; Lead; Microscopic; Molecular; Play; Proteins; Proviruses; RNA; RNA Splicing; Resolution; Roentgen Rays; Role; Structural Biologist; Structure; Techniques; Translations; Viral; Virus Replication; base; clinically relevant; design; human disease; insight; multidisciplinary; novel; novel strategies; particle; protein function; protein structure; trafficking; viral RNA

The Center for HIV RNA Studies (CRNA) will focus on determining the structural and mechanistic bases of HIV-1 RNA dependent replication functions at the cellular, viral and atomic levels. Although considerable progress has been made over the past 25 years in understanding how proteins function in HIV-1 replication, comparatively little is known about how HIV-1 RNA structure, dynamics, trafficking, and interactions with proteins enable virus replication. Although HIV-1 RNA is exceptionally rich in biological functions, the paucity of detailed mechanistic insight into how these biological functions are executed is due to inherent difficulties in studying the structure and dynamics of RNA molecules. For example, it has been challenging to obtain high-resolution structural information for RNA and protein-RNA complexes using traditional X-ray crystallographic, NMR or cryo-electron microscopic approaches. It has also been difficult to study the functions and interactions of RNA molecules with proteins in vitro and in cells. The CRNA consists of a multidisciplinary team of structural biologists, chemists, cell and computational biologists, molecular biologists and virologists, many of whom are leaders in the study of HIV-1 RNA and the role of its structures in virus replication. They have developed and will further advance new 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 restriction factors. The studies proposed herein will enable the CRNA to advance goals of clinical relevance, including the development of novel antiviral compounds, design of new strategies for the reactivation of latent proviruses, and the augmentation of host defenses against HIV infection. These studies will also result in the development of novel techniques that can be applied to all areas of RNA biology.

HIV RNA 研究中心 (CRNA) 将重点确定 HIV RNA 研究的结构和机制基础 HIV-1 RNA 依赖性复制在细胞、病毒和原子水平上发挥作用。虽然相当可观 过去 25 年在理解蛋白质如何在 HIV-1 复制中发挥作用方面取得了进展， 对于 HIV-1 RNA 的结构、动力学、运输以及与 HIV-1 RNA 的相互作用的了解相对较少 蛋白质使病毒能够复制。尽管 HIV-1 RNA 具有异常丰富的生物学功能，但其缺乏 对这些生物功能如何执行的详细机制的了解是由于固有的困难 研究RNA分子的结构和动力学。例如，获得 使用传统 X 射线获取 RNA 和蛋白质-RNA 复合物的高分辨率结构信息 晶体学、核磁共振或冷冻电子显微镜方法。研究也遇到了困难 RNA分子在体外和细胞内的功能和与蛋白质的相互作用。 CRNA 由 由结构生物学家、化学家、细胞和计算生物学家、分子生物学家组成的多学科团队 生物学家和病毒学家，其中许多人是 HIV-1 RNA 及其结构作用研究的领导者 在病毒复制过程中。他们已经开发并将进一步推进新方法来克服当前的问题 技术障碍，能够机械确定 HIV-1 RNA 结构的作用和 病毒转录、剪接、翻译、包装、颗粒组装和相互作用中的相关蛋白 有限制因素。本文提出的研究将使 CRNA 能够推进临床目标 相关性，包括开发新型抗病毒化合物、设计新策略 潜伏原病毒的重新激活，以及增强宿主对艾滋病毒感染的防御。这些研究 还将导致可应用于 RNA 生物学所有领域的新技术的发展。