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.

计划概要 将组建猎豹艾滋病毒感染、限制和病毒动力学结构生物学中心 围绕：1）三个科学项目将增进我们对艾滋病毒宿主相互作用的理解并提供基础 用于开发艾滋病毒治疗和治愈的新治疗策略，2) 三个科学核心将推动重要的进展 方法并为中心成员提供最先进的技术，3) 一个管理核心，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) 发展核心将吸引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）将在分子和病毒方面定义 HIV-1 生命周期前半部分的步骤。 机械细节。 科学项目 2（针对 HIV 的先天细胞防御）将定义宿主的结构和机制基础 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 跨多个尺寸和分辨率尺度的动态；来自整体动物研究，这些研究将对以下部位进行成像和表征 细胞和组织水平上的病毒反弹、原病毒沉默和重新激活的结构研究、 尝试创建新的泛热带块来包膜病毒出芽和新的生物制剂输送系统。 科学核心 1（生物聚合物合成和筛选工具）将开发新方法并提供中心 成员可以使用最先进的仪器和肽合成、蛋白质设计和 CRISPR 方面的专业知识 筛选方法。 科学核心 2（结构和机制研究工具）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， 用于结构测定和电子冷冻断层扫描的支架。 科学核心 3（蛋白质生产、生物物理表征和结构测定）将提供 蛋白质和复合物表达和纯化、生物物理方面最先进的仪器和专业知识 通过 X 射线晶体学和冷冻电镜进行表征和结构测定。 我们的行政核心将协调中心的全部活动；监测进展情况，并确保所有 人员、项目和核心正在有效运作。该核心还将监督中心的组织和治理， 科学教育和公共宣传，包括我们屡获殊荣的艾滋病毒科学网站和相关媒体。 我们的发展核心将管理我们的协作发展、研讨会、访问学者和其他培训 早期职业调查员的活动。