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）将集中于确定结构和机械基础 HIV-1 RNA依赖性复制在细胞，病毒和原子水平上的功能。虽然很大 在过去的25年中，取得了进步，以了解蛋白质在HIV-1复制中的作用， 关于HIV-1 RNA结构，动力学，运输和与与 蛋白质可以复制病毒。尽管HIV-1 RNA异常富含生物学功能，但缺乏 关于这些生物学功能如何执行的详细机械洞察力是由于固有的困难 在研究RNA分子的结构和动力学时。例如，获得 使用传统X射线的RNA和蛋白RNA复合物的高分辨率结构信息 晶体学，NMR或冷冻电子微观方法。研究 RNA分子与蛋白质在体外和细胞中的功能和相互作用。 CRNA由 结构生物学家，化学家，细胞和计算生物学家的多学科团队，分子 生物学家和病毒学家，其中许多是HIV-1 RNA研究的领导者及其结构的作用 在病毒复制中。他们已经开发并将进一步推进新的方法来克服当前 技术障碍，能够确定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的相关蛋白质 与限制因素。本文提出的研究将使CRNA能够促进临床目标 相关性，包括开发新型抗病毒化合物，新策略的设计 潜在病毒的重新激活，并增强宿主防御艾滋病毒感染。这些研究 还将导致可以应用于RNA生物学所有领域的新技术的发展。