Biochemical and structural mechanisms at the filoviral-host interface
Biochemical and structural mechanisms at the filoviral-host interface
批准号:
10555055
负责人:
Gaya K. Amarasinghe
金额:
$111.25万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-07-07 至 2028-05-31
关键词:
ActinsAddressAfricaAntiviral AgentsBiochemicalBiochemistryBiologyCOVID-19 pandemicCellsClustered Regularly Interspaced Short Palindromic RepeatsCommunicable DiseasesComplementComplexCore ProteinCryo-electron tomographyCryoelectron MicroscopyCytoskeletonDataDevelopmentDiseaseDisease OutbreaksEbola virusEventFamilyFilovirusGenetic TranscriptionGenomeHealthHumanHybridsImmuneImmune responseInfectionIntegration Host FactorsKnowledgeLengthLow-Density LipoproteinsMarburgvirusMass Spectrum AnalysisMethodsMolecularNatureNucleocapsidNucleocapsid ProteinsNucleoproteinsOpen Reading FramesPathway interactionsPhysical condensationPlayPolymerasePositioning AttributePost-Translational Protein ProcessingProcessProductivityProtein-Protein Interaction MapProteinsProteomicsPublicationsPublishingRNARNA chemical synthesisRNA-Directed RNA PolymeraseRegulationResearch PersonnelResearch Project GrantsResolutionResourcesRoentgen RaysRoleSignal TransductionSmall Interfering RNAStructureTherapeuticTimeViralViral ProteinsVirusVirus DiseasesVirus ReplicationWorkX-Ray Crystallographyenzyme activityglobal healthinnovationinsightmultidisciplinarymultiple omicsnovelnucleaseparticleprotein protein interactionreceptorstructural biologytherapeutic targettoolvaccine candidateviral RNA
中文摘要
丝状病毒宿主的生物化学和结构机制
英文摘要
RP01 Project Summary/Abstract for Biochemical and structural mechanisms at the filoviral-host
interface
The recent filoviral outbreaks, including the 2013-2016 Ebola virus (EBOV) outbreak in West Africa that
introduced the virus to other continents, highlight the imminent threat to global health posed by filoviruses and
the urgent need for basic and translational efforts. The current COVID-19 pandemic further illustrates the
significance of understanding infectious diseases. While recent efforts to develop countermeasures have
resulted in vaccine candidates and some therapeutics, filoviruses remain a considerable threat to human
health and key questions are still outstanding. There are substantial gaps in our understanding of host-viral
interactions that contribute to disease, including how viral proteins limit host responses and assemble into
infectious particles. Work in Research Project 1 (RP01) will use proteomic, biochemical, and structural
methods to identify and validate molecular mechanisms at the host-viral interface in cellular networks to
address this gap. We will address these longstanding mechanistic questions using biochemical and hybrid
structural methods, including mass spectrometry, NMR, X-ray crystallography, small angle X-ray scattering
(SAXS), and cryoelectron microscopy (cryo-EM), cryoelectron tomography (cryo-TM) to characterize filoviral
nucleocapsid (NC) interactions and to define high impact filoviral-host factor interactions modulating PTMs that
impact the viral replication cycle, viral NC assembly, and egress. Our strong publication record, preliminary
results from ongoing studies, and access to unique facilities and resources support these efforts. We are
uniquely positioned due to our highly productive and collaborative team with complementary expertise and a
prior record of co-authored studies with investigators in RP02, RP03, Core B, and Core C. Our Aims are: Aim
1. Determine the structural basis and dynamics of the filoviral nucleocapsid (NC) and define NC-host
interactions; Aim 2. Develop Protein-protein interaction (PPI) maps that include post-translational modifications
(PTMs) from virally infected cells for EBOV and MARV; and Aim 3. Define the molecular mechanisms for PPIs
that contribute to filoviral infection defined by this project, RP02 and RP03. At the completion, we expect to
define filoviral interaction with host factors that contribute to filoviral infection. Our arsenal of tools from mass
spectrometry, biochemistry, and structural biology, together with work from the Research Projects and
Scientific Cores within the PPG, enable us to clearly define each contribution to filoviral infection and identify
new targets for antivirals.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Characterizing the role of LDL related receptor 1 (Lrp1) as host entry factor for multiple bunyaviruses
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批准号:10667857
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资助金额:$78.36万
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财政年份:2023
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负责人:Gaya K. Amarasinghe
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依托单位:
HSP90 paralog selective small molecules as anti-old-world alpha-viral therapeutic leads.
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批准号:10753347
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项目类别:
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资助金额:$24.77万
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财政年份:2023
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负责人:Gaya K. Amarasinghe
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依托单位:
Discovery of Bunyaviral Endonuclease Inhibitors for Antiviral Therapy
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批准号:10683329
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项目类别:
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资助金额:$27.21万
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财政年份:2022
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负责人:Gaya K. Amarasinghe
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依托单位:
Discovery of Bunyaviral Endonuclease Inhibitors for Antiviral Therapy
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批准号:10481430
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项目类别:
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资助金额:$29.65万
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财政年份:2022
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负责人:Gaya K. Amarasinghe
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依托单位:
Identification and Characterization of Entry Factors Critical for Rift Valley Fever Virus Infection and Pathogenesis
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批准号:10375591
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项目类别:
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资助金额:$74.2万
-
财政年份:2021
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Development and characterization of engineered therapeutic antibodies against SARS-CoV-2
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批准号:10865147
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项目类别:
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资助金额:$38.88万
-
财政年份:2021
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Development and characterization of engineered therapeutic antibodies against SARS-CoV-2
-
批准号:10458689
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项目类别:
-
资助金额:$64.99万
-
财政年份:2021
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Development and characterization of engineered therapeutic antibodies against SARS-CoV-2
-
批准号:10669612
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项目类别:
-
资助金额:$63.87万
-
财政年份:2021
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Identification and Characterization of Entry Factors Critical for Rift Valley Fever Virus Infection and Pathogenesis
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批准号:10573316
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项目类别:
-
资助金额:$73.95万
-
财政年份:2021
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Development and characterization of engineered therapeutic antibodies against SARS-CoV-2
-
批准号:10240126
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项目类别:
-
资助金额:$66.73万
-
财政年份:2021
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Whispering Gallery Mode Devices for the Rapid Detection of Pan-Filoviruses
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批准号:10081794
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项目类别:
-
资助金额:$29.99万
-
财政年份:2020
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Whispering Gallery Mode Devices for the Rapid Detection of Pan-Filoviruses
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批准号:10211125
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项目类别:
-
资助金额:$29.18万
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财政年份:2020
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Novel VP30-host Interactions that Negatively Regulate Ebola Virus Infection
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批准号:9765490
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项目类别:
-
资助金额:$83.27万
-
财政年份:2019
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Novel VP30-host Interactions that Negatively Regulate Ebola Virus Infection
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批准号:9882940
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项目类别:
-
资助金额:$79.64万
-
财政年份:2019
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Novel VP30-host Interactions that Negatively Regulate Ebola Virus Infection
-
批准号:10576914
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项目类别:
-
资助金额:$76.21万
-
财政年份:2019
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Novel VP30-host Interactions that Negatively Regulate Ebola Virus Infection
-
批准号:10347335
-
项目类别:
-
资助金额:$77.43万
-
财政年份:2019
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Novel VP30-host Interactions that Negatively Regulate Ebola Virus Infection
-
批准号:10721290
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项目类别:
-
资助金额:$6.12万
-
财政年份:2019
-
负责人:Gaya K. Amarasinghe
-
依托单位:
DEVELOPMENT, VALIDATION, AND OPTIMIZATION OF HTS SCREENS TARGETING NIPAH AND HENDRA VIRUS RNA SYNTHESIS
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批准号:9470967
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项目类别:
-
资助金额:$53.38万
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财政年份:2017
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Molecular Mechanisms of Filoviral-host Interactions
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批准号:10555051
-
项目类别:
-
资助金额:$335.5万
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财政年份:2016
-
负责人:Gaya K. Amarasinghe
-
依托单位:
Structural and Functional Characterization of the Ebola Virus Replication Complex
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批准号:9312729
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项目类别:
-
资助金额:$274.29万
-
财政年份:2016
-
负责人:Gaya K. Amarasinghe
-
依托单位:
海外基金