Core 4 Sali Echeverria

核心 4 萨利·埃切维里亚

• 批准号: 10506986
• 负责人: ANDREJ SALI
• 金额: $ 21.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506986
• 关键词: Affinity Chromatography; Algorithms; Architecture; Biochemical; Bioinformatics; Biology; CD4 Positive T Lymphocytes; CRISPR/Cas technology; Complex; Computer software; Cryoelectron Microscopy; Data; Data Analyses; Data Set; Deuterium; Development; Genetic; Genetic Transcription; Goals; HIV; HIV Infections; HIV-1; Heterogeneity; Human; Hydrogen; Individual; Integration Host Factors; Label; Lead; Maps; Mass Spectrum Analysis; Methods; Modeling; Molecular Conformation; Pathway interactions; Peptides; Post-Translational Protein Processing; Proteins; Proteomics; Resolution; Services; Statistical Data Interpretation; Structural Models; Structure; Systems Biology; Viral; Visualization; base; cell type; crosslink; data integration; data tools; density; flexibility; genome editing; genome-wide analysis; improved; multiple data types; mutation screening; network models; open source; particle; pathogen; protein complex; protein protein interaction; restraint; structural biology; success; tool

THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES COMPUTATIONAL CORE SUMMARY The overall goal of the Computational Core is to facilitate the analysis and interpretation of multiple data types across Projects and Cores to characterize the cellular networks, proteins, and protein complexes that influence HIV replication and latency. We will employ existing bioinformatics and systems biology approaches, as well as develop new methods to facilitate the unification of mechanistic and structural details with network biology, with a strong emphasis on the analysis and integration of data derived from proteomics, genetics, and structural biology approaches. Specifically, we will provide the tools to identify interactions of endogenous proviral and antiviral HIV-host protein complexes that have been structurally and functionally characterized by the Proteomics, Genetics, and Structural Biology Cores. This includes datasets from affinity purification mass spectrometry (AP-MS), native mass spectrometry (nMS), cross-linking mass spectrometry (XL-MS), hydrogen/deuterium exchange mass spectrometry (H/DX-MS), systematic genome editing by CRISPR-Cas9, deep mutational scanning (DMS), and cryo-electron microscopy (cryo-EM). These datasets will be analyzed separately as well as jointly, followed by visualization to gain a deeper understanding of the functional pathways that are modulated during HIV infection. Finally, we will determine the structures of HIV-human protein complexes by an integrative approach using various proteomics, genetics, structural, and biochemical data. Integrative structure determination will be performed using the open-source Integrative Modeling Platform (IMP) package developed in the Sali lab (Core Lead). We will initially focus on protein complexes containing human or simian A3Gs, and HIV-1 Vif, Rev, and Tat, followed by structure determination of HIV-human complexes identified from CD4+ T cells and structurally interrogated by the Proteomics Core.

HARC中心：艾滋病毒附件和调节复合物 计算核心 总结 计算核心的总体目标是促进多种数据类型的分析和解释 跨项目和核心，以表征细胞网络，蛋白质和蛋白质复合物， HIV复制和潜伏期。我们将采用现有的生物信息学和系统生物学方法，以及 开发新的方法，以促进统一的机制和结构细节与网络生物学， 非常重视分析和整合来自蛋白质组学，遗传学和结构的数据 生物学方法。具体来说，我们将提供工具，以确定内源性前病毒的相互作用， 抗病毒HIV-宿主蛋白复合物的结构和功能特征在于： 蛋白质组学、遗传学和结构生物学核心。这包括来自亲和纯化质量的数据集 质谱法（AP-MS），天然质谱法（nMS），交联质谱法（XL-MS）， 氢/氘交换质谱（H/DX-MS），通过CRISPR-Cas9进行的系统性基因组编辑， 深突变扫描（DMS）和冷冻电子显微镜（cryo-EM）。将对这些数据集进行分析 分别以及联合，然后可视化，以获得更深入的了解功能途径 在HIV感染过程中被调节。最后，我们将确定HIV-人蛋白的结构 复合物的综合方法使用各种蛋白质组学，遗传学，结构和生化数据。 将使用开源集成建模平台（IMP）进行集成结构确定 Sali实验室开发的软件包（核心负责人）。我们将首先集中在蛋白质复合物含有人类或 猴A3 Gs和HIV-1 Vif、Rev和达特，然后测定HIV-人复合物的结构 从CD 4 + T细胞中鉴定并通过蛋白质组学核心进行结构分析。