Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease
研究项目2:转录后调控网络在埃博拉病毒疾病发病机制中的作用
基本信息
- 批准号:10602493
- 负责人:
- 金额:$ 34.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-15 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAntisense OligonucleotidesAreaBioinformaticsCandidate Disease GeneCell physiologyCellsClustered Regularly Interspaced Short Palindromic RepeatsCollaborationsDataData AnalysesDendritic CellsDevelopmentEbola Hemorrhagic FeverEbola virusEndothelial CellsEventFilovirusGene ExpressionGenesHepatitis CHepatocyteHumanImmuneImmune ToleranceImmune responseInfectionInvestigationKnowledgeLiteratureMassive Parallel SequencingMediatingMethodsModelingModificationMolecularPathogenesisPathogenicityPathway interactionsPhenotypePost-Transcriptional RegulationProtein IsoformsPublishingRNARNA InterferenceRNA ProcessingRNA SplicingRNA-Binding ProteinsRegulationRegulator GenesResearch Project GrantsRoleSamplingT cell responseT-LymphocyteTestingTissuesTranscription ProcessTranslationsViralViral PathogenesisVirusVirus DiseasesVirus ReplicationWorkcandidate identificationcell typedata resourceexperimental studyexposed human populationin vivoinsightkidney cellknock-downknowledge integrationmRNA Translationmonocytenonhuman primatenovelposttranscriptionalprogramsproteogenomicsresponsetherapeutic RNAtranscription regulatory networktranscriptomevirtual
项目摘要
RESEARCH PROJECT 2 (RP2): PROJECT SUMMARY/ABSTRACT
This overall Program Project seeks to address a significant knowledge gap concerning Ebola virus (EBOV): how
infection leads to a pathogenic rather than protective immune response. In this project, the focus is on how EBOV
infection alters posttranscriptional gene regulation in critical immune cell types and in cells that are heavily
infected (e.g., hepatocytes). There is limited understanding of how EBOV infection impacts host gene expression
at the posttranscriptional level. Indeed, although the importance of posttranscriptional regulation in gene
expression for multiple pathogenic human viruses is evident, this level of regulation has been understudied for
filoviruses.
The central hypothesis of Research Project 2 (RP2) is that cell type-specific and gene-specific posttranscriptional
responses in EBOV disease contribute to the maladaptive phenotypes of immune cells, eventually leading to
“immune paralysis” and hyperinflammation. To address this hypothesis, we will characterize the
posttranscriptional landscape during EBOV infections of primary human immune and nonimmune cells. We will
decipher the influence of EBOV infection on host RNA processing and translation. Massively parallel sequencing
approaches made possible by the Proteogenomics Core (Core C) will be used to define RNA processing
events, RNA modifications, and mRNA translation efficiency transcriptome-wide in naïve and infected cells.
Importantly, samples generated from the same experiments in the BSL-4 Core (Core B) will be used by all three
projects and thus we plan to compare our data with that of RP1 and RP3. Data analysis, integration, and
modelling will be performed in collaboration with the Bioinformatics and Modeling Core (Core D). These
experiments will yield new insights into the effect of EBOV infection on cellular gene expression in relevant cell
types. We will also characterize the posttranscriptional landscape during EBOV infection in vivo in nonhuman
primates. Using the data from these experiments, with Core D we will construct a comprehensive model of
regulated host pathways that modulate EBOV infection in different immune cell types. This model will identify
candidate genes that represent important nodes for these pathways and thus potential vulnerabilities for EBOV.
In collaboration with Core B, this project will validate posttranscriptionally altered genes and events, and ask
whether they are functionally important to cell-type specific responses to EBOV infection.
Completion of this project will reveal new and underappreciated layers of host responses to EBOV infection, and
provide a rich data resource for the field that will lead to new hypotheses to address the molecular basis for
EBOV pathogenesis. Moreover, we will identify critical new host and/or viral targets that can be exploited to
disrupt the pathogenicity of this deadly virus.
研究项目2 (rp2):项目摘要/摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Mariano A. Garcia-Blanco其他文献
Protein–protein interactions and 5'-splice-site recognition in mammalian mRNA precursors
哺乳动物 mRNA 前体中的蛋白质-蛋白质相互作用和 5'-剪接位点识别
- DOI:
10.1038/368119a0 - 发表时间:
1994-03-10 - 期刊:
- 影响因子:48.500
- 作者:
Jhumku D. Kohtz;Sharon F. Jamison;Cindy L. Will;Ping Zuo;Reinhard Lührmann;Mariano A. Garcia-Blanco;James L. Manley - 通讯作者:
James L. Manley
867. Spliceosome Mediated RNA Trans-Splicing To Increase Blood Levels of Apolipoprotein A-I and High Density Lipoproteins
- DOI:
10.1016/j.ymthe.2006.08.955 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Madaiah Puttaraju;Jun Wang;Alan T. Remaley;Bryan H. Brewer;Mariano A. Garcia-Blanco;Gerard J. McGarrity - 通讯作者:
Gerard J. McGarrity
868. Novel Strategies To Inhibit Ocular Neovascularization Based on Sonic Hedgehog Pathway Blockade
- DOI:
10.1016/j.ymthe.2006.08.956 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Madaiah Puttaraju;Jun Wang;Alan T. Remaley;Bryan H. Brewer;Mariano A. Garcia-Blanco;Gerard J. McGarrity - 通讯作者:
Gerard J. McGarrity
Broad-spectrum antiviral ferruginol analog affects the viral proteins translation and actin remodeling during dengue virus infection
广谱抗病毒铁醇类似物影响登革热病毒感染期间的病毒蛋白翻译和肌动蛋白重塑
- DOI:
10.1016/j.antiviral.2025.106139 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:4.000
- 作者:
Vicky C. Roa-Linares;Liliana A. Betancur-Galvis;Miguel A. González-Cardenete;Mariano A. Garcia-Blanco;Juan C. Gallego-Gomez - 通讯作者:
Juan C. Gallego-Gomez
Host RNA-binding proteins and specialized viral RNA translation mechanisms: Potential antiviral targets
宿主 RNA 结合蛋白和专门的病毒 RNA 翻译机制:潜在的抗病毒靶点
- DOI:
10.1016/j.antiviral.2025.106142 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:4.000
- 作者:
Leandro Fernández-García;Mariano A. Garcia-Blanco - 通讯作者:
Mariano A. Garcia-Blanco
Mariano A. Garcia-Blanco的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Mariano A. Garcia-Blanco', 18)}}的其他基金
Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease
研究项目2:转录后调控网络在埃博拉病毒疾病发病机制中的作用
- 批准号:
10188760 - 财政年份:2021
- 资助金额:
$ 34.54万 - 项目类别:
Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease
研究项目2:转录后调控网络在埃博拉病毒疾病发病机制中的作用
- 批准号:
10394321 - 财政年份:2021
- 资助金额:
$ 34.54万 - 项目类别:
Consequences and mechanism of aberrant splicing in African American prostate cancer disparities
非裔美国人前列腺癌差异中异常剪接的后果和机制
- 批准号:
9884534 - 财政年份:2017
- 资助金额:
$ 34.54万 - 项目类别:
Consequences and mechanism of aberrant splicing in African American prostate cancer disparities
非裔美国人前列腺癌差异中异常剪接的后果和机制
- 批准号:
10116165 - 财政年份:2017
- 资助金额:
$ 34.54万 - 项目类别:
Fourth Pan American Dengue Research Network Meeting
第四届泛美登革热研究网络会议
- 批准号:
8836790 - 财政年份:2014
- 资助金额:
$ 34.54万 - 项目类别:
Targeting host 3'-5' exonucleases required for flaviviral infection
靶向黄病毒感染所需的宿主 3-5 核酸外切酶
- 批准号:
8540496 - 财政年份:2012
- 资助金额:
$ 34.54万 - 项目类别:
IsoCyte Laser Scanning Plate Cytometer for High-throughput, High-content Assays
IsoCyte 激光扫描板细胞仪用于高通量、高内涵分析
- 批准号:
8052318 - 财政年份:2011
- 资助金额:
$ 34.54万 - 项目类别:
Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors
前列腺肿瘤中的选择性剪接和上皮间质可塑性
- 批准号:
7991827 - 财政年份:2008
- 资助金额:
$ 34.54万 - 项目类别:
Integrated instrument system for maintenance and delivery of RNAi libraries
用于维护和交付 RNAi 文库的集成仪器系统
- 批准号:
7388756 - 财政年份:2008
- 资助金额:
$ 34.54万 - 项目类别:
Alternative splicing and epithelial-mesenchymal plasticity in prostate tumors
前列腺肿瘤中的选择性剪接和上皮间质可塑性
- 批准号:
8196869 - 财政年份:2008
- 资助金额:
$ 34.54万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 34.54万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 34.54万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 34.54万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 34.54万 - 项目类别:
Studentship