Core 4 Sali Echeverria

核心 4 萨利·埃切维里亚

• 批准号: 10666663
• 负责人: ANDREJ SALI
• 金额: $ 19.7万
• 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/10666663
• 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; 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; structural determinants; 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.

硬中心：HIV附属和调控复合物