Project 2: Systems biology analyses of RHCMV/SIV and IL-15 mechanisms of immune programming
项目2:RHCMV/SIV和IL-15免疫编程机制的系统生物学分析
基本信息
- 批准号:10723640
- 负责人:
- 金额:$ 32.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressBioinformaticsBloodCD8-Positive T-LymphocytesCellsCellular Indexing of Transcriptomes and Epitopes by SequencingComputer AnalysisCoupledCytomegalovirusData SetGene ExpressionGenesGoalsGut associated lymphoid tissueHIV AntigensHIV vaccineHumanImmuneImmune responseImmune signalingImmunityIn VitroInfectionInflammatoryInterceptInterferonsInterleukin-15KnowledgeLinkLymphoid TissueMacaca mulattaMediatingMitogen-Activated Protein KinasesModelingMolecularMucous MembranePathogenicityPathway interactionsPeripheral Blood Mononuclear CellPhenotypeProductionResearch DesignRhesusSIVSIV VaccinesSignal PathwaySignal TransductionSiteStatistical Data InterpretationSystemSystems BiologyT-LymphocyteTissuesTranslatingVaccinatedVaccinationVaccinesViralViral AntigensVirusVirus DiseasesWhole BloodWorkcell typecohortfunctional genomicsgene networkgenomic dataimmune activationin vivolymph nodesmonocytenano-stringpredictive markerpredictive signatureprogramsresponsesingle-cell RNA sequencingsuccesstranscription factortranscriptometranscriptome sequencingtranscriptomicstreatment responsevaccine efficacyvaccine responsevaccinologyvectorvector-based vaccine
项目摘要
Project 2 brings a systems biology approach, “systems vaccinology”, to investigate immune response
programing by IL-15 and RhCMV/SIV vaccine. Our goal is to define the molecular response by which IL-15 and
RhCMV/SIV vaccine program the protection-predictive immune phenotype in whole blood to vaccination, what
we term as the “whole blood protection-predictive transcriptomic signature” [wbPPTS] that predicts and underlies
vaccine protection from SIV infection. We will conduct three Aims including i) Determine the response to IL-15
in monocytes and T cells; ii) Define the tissue and cell-specific transcriptome correlates of IL-15 signaling linked
with RhCMV/SIV vaccination phenotype to program the wbPPTS, and iii) Validate RhCMV/SIV vaccination tissue
and wbPPTS signature linkage with protection against SIV challenge. Our research design features in vitro and
ex vivo models for analyses of cell signaling/responses to IL-15, and in vivo analyses of cell and tissue application
of three "omics" platforms including single cell RNA sequencing (scRNAseq and CITEseq), bulk RNAseq, and
tissue spatial profiling. Our bioinformatics/computational analyses will integrate functional genomics data sets
with immune response and protection phenotypes to determine the molecular and cellular features directing the
wbPPTS and vaccine protection. We will conduct bioinformatics of RhCMV/SIV transcriptomic responses in an
independent vaccination/SIV challenge cohort to ascertain specific tissue signature of protection and the
wbPPTS. This work will be conducted in a collaborative framework conjunction with Cores A-C and Project 1.
项目2带来了系统生物学的方法,“系统疫苗学”,研究免疫反应
用IL-15和RhCMV/SIV疫苗编程。我们的目标是确定IL-15和
RhCMV/SIV疫苗程序的保护预测免疫表型在全血接种,什么
我们称之为“全血保护-预测转录组签名”[wbPPTS],它预测并支持
预防SIV感染的疫苗。我们将进行三个目标,包括i)确定对IL-15的反应
ii)定义IL-15信号传导相关的组织和细胞特异性转录组相关物;
使用RhCMV/SIV疫苗接种表型对wbPPTS进行编程,以及iii)验证RhCMV/SIV疫苗接种组织
以及具有针对SIV挑战的保护的wbPPTS签名链接。我们的研究设计特点是在体外,
用于分析细胞信号传导/对IL-15的应答的离体模型,以及细胞和组织应用的体内分析
三个“组学”平台,包括单细胞RNA测序(scRNAseq和CITEseq),批量RNAseq,
组织空间分布我们的生物信息学/计算分析将整合功能基因组学数据集
与免疫应答和保护表型,以确定分子和细胞特征,指导
wbPPTS和疫苗保护。我们将进行RhCMV/SIV转录组反应的生物信息学研究,
独立的疫苗接种/SIV攻毒队列,以确定特定的保护组织特征,
wbPPTS。这项工作将在与核心A-C和项目1合作的框架内进行。
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)
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Michael Gale其他文献
Michael Gale的其他文献
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{{ truncateString('Michael Gale', 18)}}的其他基金
MECHANISMS PROGRAMMING PROTECTIVE IMMUNITY FROM RhCMV-SIV VACCINE AND IL-15 ACTIONS
RhCMV-SIV 疫苗和 IL-15 作用的保护性免疫编程机制
- 批准号:
10723635 - 财政年份:2023
- 资助金额:
$ 32.77万 - 项目类别:
Omics, Bioinformatics, and Data Management Core
组学、生物信息学和数据管理核心
- 批准号:
10709011 - 财政年份:2022
- 资助金额:
$ 32.77万 - 项目类别:
Omics, Bioinformatics, and Data Management Core
组学、生物信息学和数据管理核心
- 批准号:
10619301 - 财政年份:2022
- 资助金额:
$ 32.77万 - 项目类别:
University of Washington Arboviral Research Network (UWARN)
华盛顿大学虫媒病毒研究网络 (UWARN)
- 批准号:
10687434 - 财政年份:2022
- 资助金额:
$ 32.77万 - 项目类别:
University of Washington Arboviral Research Network (UWARN)
华盛顿大学虫媒病毒研究网络 (UWARN)
- 批准号:
10493552 - 财政年份:2021
- 资助金额:
$ 32.77万 - 项目类别:
Host inflammatory response to SARS-CoV-2
宿主对 SARS-CoV-2 的炎症反应
- 批准号:
10192439 - 财政年份:2021
- 资助金额:
$ 32.77万 - 项目类别:
University of Washington Arboviral Research Network (UWARN)
华盛顿大学虫媒病毒研究网络 (UWARN)
- 批准号:
10770598 - 财政年份:2020
- 资助金额:
$ 32.77万 - 项目类别:
University of Washington Arboviral Research Network (UWARN)
华盛顿大学虫媒病毒研究网络 (UWARN)
- 批准号:
10170249 - 财政年份:2020
- 资助金额:
$ 32.77万 - 项目类别:
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