Behavior of HIV in viral environments (b-hive)

Active Cooperative Agreement Awarded Last action

Award ID
U54AI170855
Recipient
Awarding agency
Obligated
$81,192,116

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 91% complete
Funding
  • $74,903,072.00 Federal
  • $6,289,044.00 Non-federal
Place of performance
Seattle, WA 98101, USA

Award details come from USAspending.gov.

Description

Abstract
, overview the behavior of HIV in viral environments (b-hive) center has been formed to further the understanding of HIV-1 and HIV-1/cellular host factor macromolecular interactions within distinct cellular environments, which shape the HIV replication cycle. With the limited size of HIV's RNA genome, IT is no surprise that many of the same gene products end up performing different functions in different cellular environments at different times during replication. These various HIV-1-cell host factor interactions promote the cellular pathogenesis, and ultimately disease, characteristic of HIV-1/aids. All members have joined the b-hive center with the common goal to collaboratively investigate the dynamic HIV-1 and HIV-1/cellular host factor macromolecular interactions within distinct cellular environments that occur during infection. The b-hive center will capitalize on well- established collaborations between top HIV researchers and scientific accomplishments that provide the rationale to ask new and challenging questions and will be informed by the former hive center (HIV interaction and viral evolution), an organizational structure proven to be effective at not only HIV-1 research, but also by exemplary communication to training, and outreach activities. The b-hive team of highly collaborative investigators includes well-established experts in structural, biophysical, chemical, and computational biology, virology, and synthetic chemistry. Only as a center do the researchers have the necessary combined expertise and critical mass to effectively study the dynamic and mechanistic implications of macromolecular interactions of HIV and cellular host factors within distinct cellular environments. The overall aims of the b-hive are organized around three complementary projects that focus on specific stages of the viral replication cycle: project 1. Dynamic HIV-1 core interactions with host factors and inhibitors from cytoplasm to nucleus. Aim 1. To discover and characterize novel, dynamic interactions between HIV-1 CA and host cell during virus ingress. Aim 2. To characterize interactions of novel small molecule inhibitors with distinct sites on HIV-1 CA. Project 2. Structural dynamics of HIV-1 nuclear trafficking, integration, and transition to transcription. AIM1. Elucidate dynamic HIV-1 core-host cell interactions crucial for nuclear trafficking, uncoating, and integration. Aim 2. Define the structural and dynamic nuclear events underlying HIV-1 integration site selection. Aim 3. Determine the interplay between integration site and transcriptional latency. Project 3. The dynamics of HIV-1 packaging and assembly. Aim 1. Study the mechanism of HIV-1 RNA genome packaging and the proteins complexed with HIV-1 RNA. Aim 2. Probe the cellular dynamics of the interactions between HIV-1 GAG and identified cellular factors that alter HIV-1 production. Aim 3. Elucidate the dynamics of model GAG assembly and particle formation.

Transactions

Action Federal Non-federal Date
Amendment $5,819,586 $0
Amendment $5,862,824 $0
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Amendment Experimental characterization and computational modeling of intrinsic bioreactivity of sufex/covalent nucleophile warheads $253,415 $0
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Amendment $5,911,895 $0
Amendment Experimental characterization and computational modeling of intrinsic bioreactivity of sufex/covalent nucleophile warheads $5,911,895 $0
Amendment $5,911,895 $0
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Amendment Experimental characterization and computational modeling of intrinsic bioreactivity of sufex/covalent nucleophile warheads $0 $0
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Amendment $802,451 $0
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Amendment $5,956,849 $0
Amendment $5,956,849 $0
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Amendment $5,956,849 $0
Amendment $6,289,044 $0
Original award $6,289,044 $6,289,044
Show all 25

Subawards

Subrecipient Amount Awarded
Florida State University Dr. Francis’ lab in the Department of Biological Science and in the Institute of Molecular Biophysics in Florida State University will actively participate in… $89,209
Rutgers The State University Of New Jersey Dr. Eddy Arnold is involved in design and coordination of experiments, communication with collaborators, presentation of research results at scientific… $240,530
Emory University This proposal tackles important gap in HIV integration on the genome and the role of non-B form nucleic acids in integration site selection. This process is… $108,333
Georgia TECH Research Corp The Finn laboratory will bring advanced bioconjugation expertise to bear for the design and preparation of protein nanoparticle-based immunogens. Our focus will… $152,331
Scripps Research Institute We propose to construct detailed, integrated atomic models of the HIV virion at various stages of its life cycle using our cellPACK ecosystem, leveraging data… $108,333
Scripps Research Institute For this Collaborative Development Project (CDP) proposal, the Ken Lab will use its expertise in characterizing viral RNA structure and function through… $108,333
King's College London 1. Apply their recently developed knowledge of the role of MX2 phosphorylation/ dephosphorylation to identify the cellular kinase(s) that phosphorylates the… $56,385
Emory University The Sarafianos lab will: • Perform protein expression and purification, biochemical, biophysical, virological, and structural studies (X-ray Crystallography and… $297,248
Emory University Dr. Kirby is a co-Lead of the B-HIVE Development Core. She will lead the CDP and training efforts of the B-HIVE Development Core in collaboration with Dr.… $48,579
Emory University Dr. Kirby also has administrative duties as a co-Assistant Program Manager of B-HIVE. These include: • Dr. Kirby will provide scientific Center support to the… $147,346
Emory University Work in the Melikian lab will be divided between Project 1 (collaboration with co-leads Kvaratskhelia and Sarafianos), Project 3 (collaboration with co-lead… $165,518
Emory University Crye-Electron Tomography and subtomogram averaging component of the structure core. The goal of this work is to determine how HIV capsid binding compounds alter… $192,508
The University Of Chicago Project 1 The HIV-1 capsid lattice interacts with various small molecules and proteins, which are crucially important for understanding HIV-1 biology and… $250,261
University Of Florida Dr. Griffin and colleagues at Scripps Florida will use hydrogen/deuterium exchange mass spectrometry (HDXMS), crosslinking mass spectrometry (XL-MS) and… $214,197
Temple University-Of The Commonwealth System Of Higher Education Ronald M. Levy is a member of the Computational Core. He will use all atom molecular dynamics simulations and sequence-covariation methods to understand and… $117,101
Scripps Research Institute Dr. Millar and his team will support the goals of the B-HIVE center in two ways: (1) As co-lead of the Biophysics Core and (2) as active participants in Project… $267,299
Scripps Research Institute Dr. Forli will Co-Lead the Computational Core to provide structure-based support for the research Projects of the Center. The lab will provide rapid… $255,039
Scripps Research Institute Dr. Williamson will be responsible for overall direction of the project, including conception, design, and implementation of the experiments, analysis of the… $273,981
Scripps Research Institute Prof. Olson will serve as the Scientific Coordinator for the B-HIVE Center. In conjunction with the Center Directors, he will oversee and coordinate the… $87,426
Scripps Research Institute Sequencing Core for the U54 BHIVE (Behaviour of HIV in Viral Environments) Center Next-Generation Sequencing is an essential and fundamental approach in… $186,297
Dana-Farber Cancer Institute, Inc. Dr. Engelman will participate as a sub-contractor Principal Investigator on the B-HIVE U54 application, PIs Stefan Sarafianos, Ph.D. and Bruce Torbett, Ph.D.… $336,740
Vanderbilt University My lab provides NMR spectroscopy technology expertise and service to the Behavior of HIV in Viral Environments (B-HIVE) center. We consult with other B-HIVE… $81,413
The Salk Institute For Biological Studies. San Diego. California Dr. Lyumkis’ group is using high-resolution cryo-EM to understand macromolecular structure, assembly, and function pertinent to the HIV replication cycle. His… $423,818
Florida State University Dr. Francis' lab in the Department of Biological Science and in the Institute of Molecular Biophysics in Florida State University will actively participate in… $91,020
The Regents Of The University Of Colorado Dr. Kvaratskhelia will participate in the 8-HIVE Center application as a Project 1 Co-Lead together with Dr. Sarafianos. Furthermore, Dr. Kvaratskhelia will… $342,472
The Ohio State University Musier-Forsyth will contribute to studies described in Project 3, Aims 1 and 3 and Core 3, Aims 2 and 3. She will also co-direct Core 3. Musier-Forsyth’s lab… $260,238
Rutgers The State University Of New Jersey Dr. Eddy Arnold is involved in design and coordination of experiments, communication with collaborators, presentation of research results at scientific… $255,638
Scripps Research Institute We will purchase the compounds to perform the experimental assessment of intrinsic reactivity of the SuFEx compounds using the proposed hydrolysis… $525,290
Emory University B-HIVE Year 3 Administrative Supplement: Developing Lenacapavir-like compounds to disruptcellular virion assembly and test whether they act as Capsid-TACKs… $253,415
The Salk Institute For Biological Studies. San Diego. California Dr. Lyumkis’ group is using high-resolution cryo-EM to understand macromolecular structure, assembly, and function pertinent to the HIV replication… $432,468
Emory University Crye-Electron Tomography and subtomogram averaging component of the structure core. The goal of this work is to determine how HIV capsid binding compounds alter… $243,582
Georgia TECH Research Corp The Finn laboratory will bring advanced bioconjugation expertise to bear for the design and preparation of protein nanoparticle-based immunogens. Our focus will… $153,870
King's College London 1. Apply their recently developed knowledge of the role of MX2 phosphorylation/ dephosphorylation to identify the cellular kinase(s) that phosphorylates the… $57,773
Dana-Farber Cancer Institute, Inc. Dr. Engelman will participate as a sub-contractor Principal Investigator on the B-HIVE U54 application, PIs Stefan Sarafianos, Ph.D. and Bruce Torbett, Ph.D.… $343,612
Scripps Research Institute Prof. Olson will serve as the Scientific Coordinator for the B-HIVE Center. In conjunction with the Center Directors, he will oversee and coordinate the… $87,865
Vanderbilt University My lab provides NMR spectroscopy technology expertise and service to the Behavior of HIV in Viral Environments (B-HIVE) center. We consult with other B-HIVE… $96,025
Scripps Research Institute Sequencing Core for the U54 BHIVE (Behaviour of HIV in Viral Environments) Center Next-Generation Sequencing is an essential and fundamental approach in… $188,178
Scripps Research Institute Dr. Williamson will be responsible for overall direction of the project, including conception, design, and implementation of the experiments, analysis of the… $289,336
Emory University The Sarafianos lab will: • Perform protein expression and purification, biochemical, biophysical, virological, and structural studies (X-ray… $303,315
University Of Florida Dr. Griffin and colleagues at Scripps Florida will use hydrogen/deuterium exchange mass spectrometry (HDX-MS), crosslinking mass spectrometry (XL-MS) and… $274,081
Emory University Work in the Melikian lab will be divided between Project 1 (collaboration with co-leads Kvaratskhelia and Sarafianos), Project 3 (collaboration with co-lead… $170,224
Scripps Research Institute Dr. Millar and his team will support the goals of the B-HIVE center in two ways: (1) As co-lead of the Biophysics Core and (2) as active participants in Project… $293,999
Temple University-Of The Commonwealth System Of Higher Education Ronald M. Levy is a member of the Computational Core. He will use all atom molecular dynamics simulations and sequence-covariation methods to understand and… $117,689
The University Of Chicago The HIV-1 capsid lattice interacts with various small molecules and proteins, which are crucially important for understanding HIV-1 biology and developing new… $255,369
Florida State University Dr. Francis' lab in the Department of Biological Science and in the Institute of Molecular Biophysics in Florida State University will actively participate in… $99,851
The Ohio State University Musier-Forsyth will contribute to studies described in Project 3, Aims 1 and 3 and Core 3, Aims 2 and 3. She will also co-direct Core 3. Musier-Forsyth’s… $265,549
Scripps Research Institute Dr. Forli will Co-Lead the Computational Core to provide structure-based support for the research Projects of the Center. The lab will provide rapid… $260,243
University Of North Carolina At Chapel Hill Brain microglia (MG) may serve as a true stable HIV reservoir in the central nervous system (CNS). To understand the mechanisms behind such stable reservoirs,… $108,333
Scripps Research Institute We propose to construct detailed, integrated atomic models of the HIV virion at various stages of its life cycle using our cellPACK ecosystem, leveraging data… $108,333
Emory University NIH U54, Behavior of HIV in Viral Environments (B-HIVE Center), Years 1-5 • Dr. Kirby is a co-Lead of the B-HIVE Development Core. She will lead the CDP… $48,824
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Quick answers

Who received award U54AI170855?

U54AI170855 was awarded to Seattle Children's Hospital by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 22, 2022.

How much is award U54AI170855 worth?

$81,192,116 has been obligated on U54AI170855: $74,903,072 in federal funding and $6,289,044 in non-federal funding.

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