HARC Center: HIV Accessory and Regulatory Complexes

HARC 中心：HIV 辅助和调节复合体

• 批准号: 9410900
• 负责人: Nevan J Krogan
• 金额: $ 484.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-27 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9410900
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Antibodies; Biological; Biological Assay; Biology; CRISPR/Cas technology; Cell physiology; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Complement; Complex; Cryoelectron Microscopy; DNA; Detection; Development; Electron Microscopy; Ensure; Enzymes; Event; Evolution; Funding Opportunities; Genetic; Genetic Transcription; Genetic study; Goals; HIV; HIV-1; Host Defense; Human; In Vitro; Individual; Interdisciplinary Study; Intervention; Label; Laboratories; Lead; Learning; Life Cycle Stages; Light; Lipids; Mass Spectrum Analysis; Membrane; Membrane Lipids; Membrane Proteins; Methodology; Methods; Mission; Modeling; Molecular; Mutation; Nucleic Acids; Other Genetics; Pathogenesis; Pathway interactions; Patients; Peptides; Peroxidases; Pharmaceutical Preparations; Positive Transcriptional Elongation Factor B; Post-Translational Protein Processing; Program Development; Proteins; Proteomics; RNA; Regimen; Regulation; Research; Research Personnel; Residencies; Resolution; Resources; Roentgen Rays; Scientist; Seeds; Series; Sister; Source; Structure; System; T-Lymphocyte; TNFRSF5 gene; Techniques; Technology; Therapeutic; Therapeutic Intervention; Traction; Training; Ubiquitination; Validation; Viral; Virus; Work; X-Ray Crystallography; ascorbate; beamline; cofactor; cohort; data sharing; drug efficacy; flexibility; genetic approach; genetic information; genetic regulatory protein; improved; in vivo; innovation; insight; member; molecular imaging; nanodisk; nef Protein; new technology; next generation; novel; novel therapeutic intervention; outreach; programs; protein complex; protein expression; resistance mutation; rev Protein; scaffold; screening; structural biology; symposium; tat Protein; technology training; therapeutic target; titanium dioxide; tool; trafficking; treatment strategy; vif Gene Products; virology; virus genetics; vpu Protein

CENTERS FOR HIV/AIDS-RELATED STRUCTURAL BIOLOGY (P50) HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES OVERALL SUMMARY The HARC Center is an integrated program proposed by investigators whose overarching goal is to improve understanding of the interactions between HIV accessory and regulatory proteins and host cellular systems to enable eventual expansion of therapeutic approaches. There are currently no HIV therapeutics targeting any of the proteins on which the HARC Center is focused (HIV-1 Vif, Vpu, Nef, Tat and Rev proteins and their interacting viral and cellular partners). The scientific focus of the Center is on determining structures of these complexes, using an integrated Systems to Structure pipeline that includes (1) Discovery, through novel methods of functional proteomics and genetics being developed in the HARC Center, (2) Validation through breakthrough CRISPR methods in primary T cells as well as targeted in vivo and in vitro functional assays, and (3) Structure Determination using a synthesis of innovative structural techniques developed in the HARC Center to address the large, flexible, heterogeneous and sometimes membrane-associated systems we study. We are focused on two themes aimed at understanding the biological questions surrounding HIV replication and persistence in the host cell. These include how the virus counteracts host restriction mechanisms (Theme 1: “Counteracting”) and how the virus hijacks host systems for viral transcription and RNA export/trafficking to ensure continuation of the viral life cycle (Theme 2: “Hijacking”). The seven projects proposed here include: (1) Structure and Evolution of APOBEC3-Vif Interactions, (2) Regulation of Vif and Rewiring of Host Pathways, (3) The Multiple Functions of Vpu at the Membrane, (4) Nef Interaction Networks at the Membrane, (5) Tat-Host Transcription Complexes, (6) Structure and Dynamics of Rev and RNA-Host Complexes, and (7) Characterization of “Super Restriction Factors” and Prediction of Host-HIV Interfaces. The HARC Center projects are supported by an administrative core and seven technology cores essential for their completion: (1) Proteomic Approaches to HIV Function, (2) CRISPR in Primary Cells to Study HIV-Host Function, (3) Molecular Imaging Using Cryo-Electron Microscopy (EM), (4) Application and Development of Antibody Tools, (5) Integrative Modeling of HIV-Human Complexes, (6) X-ray Screening and Rapid Structure Determination, and (7) Membrane Protein Expression/Purification. We are committed to collaborating with Sister Centers and the HIV research community as well as training the next generation of investigators. We create and support opportunities including the Technology Training Residency to bring young investigators to learn in our Center's Cores, and we seed new research through the Collaborative Opportunity Fund, along with holding events such as seminars and an annual symposium.

艾滋病毒/艾滋病相关结构生物学中心（p50）