The Center for HIV RNA Studies (CRNA)

HIV RNA 研究中心 (CRNA)

• 批准号: 9132305
• 负责人: KWAKU DAYIE
• 金额: $ 9.37万
• 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/9132305
• 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）将专注于确定HIV的结构和机制基础。 HIV-1 RNA依赖性复制在细胞、病毒和原子水平发挥作用。虽然相当多的 在过去的25年里，在理解蛋白质在HIV-1复制中的功能方面取得了进展， 相对而言，对HIV-1 RNA的结构、动力学、运输以及与病毒的相互作用知之甚少。 蛋白质使病毒能够复制。虽然HIV-1 RNA具有非常丰富的生物学功能，但其缺乏的生物学功能是非常重要的。 对这些生物功能是如何执行的详细的机械见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 利用传统X射线获得RNA和蛋白质-RNA复合物的高分辨率结构信息 晶体学、NMR或低温电子显微镜方法。也很难研究 RNA分子在体外和细胞中与蛋白质的功能和相互作用。CRNA由一个 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、 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 在病毒复制中。他们已经制定并将进一步推进新的方法，以克服目前的 技术障碍，使得能够机械地确定HIV-1 RNA结构的作用， 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，包括开发新的抗病毒化合物，设计新的战略， 重新激活潜伏的前病毒，增强宿主对HIV感染的防御。这些研究 也将导致新技术的发展，可应用于RNA生物学的所有领域。