CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics

CHEETAH HIV 感染、限制和病毒动力学结构生物学中心

• 批准号: 10508311
• 负责人: WESLEY I. SUNDQUIST
• 金额: $ 552.3万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-11 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10508311
• 关键词: Animals; Architecture; Award; Biological Products; Biology of HIV Infection; Biopolymers; CRISPR screen; Capsid; Cells; Cryoelectron Microscopy; Development; Education; Electrons; Ensure; Fluorescence Spectroscopy; Foundations; Genome; Goals; HIV; HIV-1; Human Resources; Image; In Situ; Infection; Innate Immune Response; Life Cycle Stages; Link; Methodology; Molecular; Monitor; Nuclear; Nucleosome Core Particle; Peptide Synthesis; Production; Protein Engineering; Proteins; Proviruses; Research Personnel; Resolution; Reverse Transcription; Role; Science; Signal Transduction; Site; Structure; System; TRIM Gene; Technology; Tissues; Training Activity; Viral; Virus; X-Ray Crystallography; animation; base; biophysical properties; career; design; instrumentation; member; new technology; next generation; novel therapeutic intervention; outreach; programs; protein complex; protein purification; reconstitution; scaffold; screening; structural biology; synergism; tool; viral rebound; virus envelope; visiting scholar; web site

PROGRAM SUMMARY The CHEETAH Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics will be organized around: 1) three Scientific Projects that will advance our understanding of HIV-host interactions and provide the foundations for developing new therapeutic strategies for HIV treatment and cure, 2) three Scientific Cores that will advance important methodology and provide Center members with access to state-of-the-art technologies, 3) an Administrative Core that will coordinate Center activities and direct our Scientific Education, Public Outreach, and Molecular Animations, and 4) a Developmental Core that will engage and support the next generation of HIV structural biology researchers. Scientific Project 1 (Infecting the Cell) will define the steps in the first half of the HIV-1 life cycle in molecular and mechanistic detail. Scientific Project 2 (Innate Cellular Defenses Against HIV) will define the structural and mechanistic bases for host recognition, restriction, and innate immune responses to HIV-1. Scientific Project 3 (Multiscale Analysis and Modulation of Viral Dynamics) will characterize and modulate HIV-1 dynamics across multiple size and resolution scales; from whole-animal studies that will image and characterize sites of viral rebound at the cellular and tissue levels, to structural studies of proviral silencing and reactivation, to studies that attempt to create new pantropic blocks to enveloped virus budding and new biologics delivery systems. Scientific Core 1 (Tools for Biopolymer Synthesis and Screening) will develop new methodology and provide Center members with access to state-of-the-art instrumentation and expertise in Peptide Synthesis, Protein Design, and CRISPR Screening Methodology. Scientific Core 2 (Tools for Structural and Mechanistic Studies) will develop new methodology and provide Center members with access to state-of-the-art instrumentation and expertise in Fluorescence Spectroscopy and Dynamics, Scaffolds for Structure Determination, and Electron Cryotomography. Scientific Core 3 (Protein Production, Biophysical Characterization, and Structure Determination) will provide access to state-of-the-art instrumentation and expertise in Expression and Purification of Proteins and Complexes, Biophysical Characterization, and Structure Determination by both X-ray crystallography and cryoEM. Our Administrative Core will coordinate the entire range of Center activities; monitoring progress, and ensuring that all Personnel, Projects, and Cores are functioning effectively. This Core will also oversee Center Organization and Governance, and Scientific Education and Public Outreach, including our award-winning Science of HIV website and associated media. Our Developmental Core will administer our Collaborative Development, Seminar, Visiting Scholar, and Other Training Activities for early career investigators.

计划摘要 将成立印度猎豹艾滋病毒感染、限制和病毒动力学结构生物学中心 围绕：1)三个科学项目，将促进我们对艾滋病毒-宿主相互作用的了解，并提供基础 为HIV治疗和治愈开发新的治疗策略，2)三个科学核心将推动重要的 方法，并为中心成员提供使用最先进技术的途径；3)将 协调中心活动并指导我们的科学教育、公共宣传和分子动画，以及4)a) 发展核心，将参与和支持下一代艾滋病毒结构生物学研究人员。 科学项目1(感染细胞)将从分子和分子水平定义HIV-1生命周期前半部分的步骤 机械化的细节。 科学项目2(针对艾滋病毒的先天细胞防御)将确定宿主的结构和机制基础 对HIV-1的识别、限制和先天免疫反应。 科学项目3(病毒动力学的多尺度分析和调节)将表征和调节HIV-1 跨多种大小和分辨率的动态；来自全动物研究，将图像和特征的地点 病毒在细胞和组织水平上的反弹，到前病毒沉默和重新激活的结构研究，到 尝试创建新的泛热带阻断包被病毒萌芽和新的生物制品输送系统。 科学核心1(生物聚合物合成和筛选工具)将开发新的方法并提供中心 成员可以使用最先进的仪器和多肽合成、蛋白质设计和CRISPR方面的专业知识 筛查方法学。 科学核心2(结构和力学研究工具)将开发新的方法并提供中心 成员可以使用最先进的仪器和荧光光谱和动力学方面的专业知识， 用于结构确定的支架和电子冷冻断层摄影术。 科学核心3(蛋白质生产、生物物理特性和结构确定)将提供 在蛋白质和复合体的表达和纯化、生物物理方面的最先进的仪器和专业知识 用X射线结晶学和低温电子显微镜对其进行了表征和结构测定。 我们的行政核心将协调中心的所有活动；监测进展，并确保所有 人员、项目和核心都在有效运作。这个核心还将监督中心的组织和治理， 以及科学教育和公众宣传，包括我们获奖的艾滋病科学网站和相关媒体。 我们的发展核心将管理我们的协作开发、研讨会、访问学者和其他培训 职业生涯早期调查人员的活动。