Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
基本信息
- 批准号:10204868
- 负责人:
- 金额:$ 32.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAgeAggressive behaviorAgingAnimal ModelAnimalsAntibodiesAntibody ResponseAntibody-Producing CellsAntigensAreaAwardCellsCharacteristicsChronicCompetitive BehaviorComplementDataDiseaseDisease susceptibilityEnvironmental MonitoringEthicsExperimental ModelsExposure toFemaleFundingGene ExpressionGene Expression RegulationGenesGenomeGenomicsGenotypeGlucocorticoidsGoalsHealthHumanIllicit DrugsImmuneImmune responseImmune systemIn VitroIndividualInequalityInfectionInflammationInfluenzaInfluenza vaccinationInnate Immune ResponseInterventionLifeLife ExpectancyLinkLipopolysaccharidesMacaca mulattaMeasuresMediatingMedicalMemoryModelingMolecularNatural ImmunityNatural Killer CellsObesityOutcomePathway interactionsPeripheral Blood Mononuclear CellPersonal SatisfactionPhysiologicalPhysiologyPositioning AttributePredictive FactorPredispositionProceduresQuantitative Trait LociRegulator GenesResearchResearch DesignRiskShapesSignal PathwaySignal TransductionSmokingSocial BehaviorSocial EnvironmentSocial GradientsSocial HierarchySocial isolationSocial statusSocial supportStressTestingTimeVaccinationVaccinesWorkadaptive immunityaffiliative behavioraging populationbehavior influencecell typecostexperienceexperimental studyhealth care availabilityhealthy aginghormonal signalsimmune functionimmune system functionimmunoregulationin vivoin vivo evaluationinfluenza virus vaccineinsightinter-individual variationlong term memorylow socioeconomic statusmembermortality risknonhuman primatepathogen exposurepredictive modelingresponsesocialsocial integrationsocial stresssocial stressorsteroid hormonestudy population
项目摘要
Project Summary
The social environment has a clear and profound impact on human health and well being. Chronic social
stress and reduced access to social support are strongly linked to major diseases of aging; as a result, social
adversity is highly predictive of life expectancy itself. Recent evidence suggests that, while some of this
relationship is explained by correlated factors such as smoking, obesity, and health care access, social
stressors also have a direct impact on physiological function. Indeed, work in animal models has clearly
demonstrated that the experience of social subordination alone can alter the function of the immune system, in
part by altering gene regulation in immune cells.
The goal of the proposed research is to address a key outstanding question that arises from these findings:
when, and for whom, are chronic social stress effects on immune function most important? To do so, it will take
advantage of dominance rank in female rhesus macaques as a model for chronic social stressor exposure in
humans. Rhesus macaque females are excellent models for human social stress because they naturally
organize into dominance rank hierarchies in which low ranking individuals experience increased rates of
harassment, reduced social affiliation, and physiological markers of rank-related stress. Importantly,
dominance rank assignments, and thus an individual's exposure to social stressors, can be manipulated in this
species by manipulating group membership. Such manipulations yield a powerful experimental model for
investigating the consequences of socially induced stress—an approach that is directly translatable to humans,
but that is practically and ethically impossible in humans themselves.
The proposed study will take advantage of this model to investigate how differential exposure to dominance
rank-induced social stress causally influences gene expression in the immune system. Specifically, it will use
an in vitro approach to efficiently screen for condition-specific social stress effects on gene expression levels
across 30 physiologically relevant environmental conditions (e.g., pathogen exposure, steroid hormone
signaling). It will complement the in vitro screen with an in vivo test of the gene regulatory and antibody
response to influenza vaccination, a medical procedure in which variable responses are of particular concern
as individuals age. Finally, it will test whether age, social behavior, and genotype can be used to predict
interindividual variation in the strength of social stressor effects on immune regulation, and hence which
individuals are most vulnerable. Together, the proposed analyses will provide much-needed insight into the
factors that explain when and why individuals differ in their response to the same social stressors, as well as
the potential consequences of these differences for medical treatment. The project's results will therefore have
direct translational application to both identifying the most susceptible members of our aging population and
suggesting tailored strategies for intervention.
项目总结
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Immunology of Stress and the Impact of Inflammation on the Brain and Behavior.
- DOI:10.1192/bja.2020.82
- 发表时间:2021-05
- 期刊:
- 影响因子:1.3
- 作者:Ravi M;Miller AH;Michopoulos V
- 通讯作者:Michopoulos V
The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease.
- DOI:10.1016/j.coi.2014.09.008
- 发表时间:2014-12
- 期刊:
- 影响因子:7
- 作者:Brinkworth, Jessica F.;Barreiro, Luis B.
- 通讯作者:Barreiro, Luis B.
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Luis Bruno Barreiro其他文献
Viral infections upregulate type-1 interferon and induce loss of oral tolerance in celiac disease
- DOI:
10.1016/j.dld.2014.07.027 - 发表时间:
2014-09-30 - 期刊:
- 影响因子:
- 作者:
Valentina Discepolo;Romain Bouziat;Jennifer Stencel;Mine Ikizler;Giuliana Lania;Merlin Nanayakkara;Alessandra Carrella;Marialaura Cuomo;Katia Ferrara;Renata Auricchio;Riccardo Troncone;Maria Vittoria Barone;Terence Dermody;Luis Bruno Barreiro;Bana Jabri - 通讯作者:
Bana Jabri
Luis Bruno Barreiro的其他文献
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{{ truncateString('Luis Bruno Barreiro', 18)}}的其他基金
Tissue destruction and healing in Celiac Disease
乳糜泻的组织破坏和愈合
- 批准号:
10518839 - 财政年份:2022
- 资助金额:
$ 32.08万 - 项目类别:
Tissue destruction and healing in Celiac Disease
乳糜泻的组织破坏和愈合
- 批准号:
10705152 - 财政年份:2022
- 资助金额:
$ 32.08万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
10155522 - 财政年份:2019
- 资助金额:
$ 32.08万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
9803109 - 财政年份:2019
- 资助金额:
$ 32.08万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
10631544 - 财政年份:2019
- 资助金额:
$ 32.08万 - 项目类别:
Characterizing the impact of Yersinia Pestis to the phenotypic evolution of the human immune system
表征鼠疫耶尔森菌对人类免疫系统表型进化的影响
- 批准号:
10403998 - 财政年份:2019
- 资助金额:
$ 32.08万 - 项目类别:
Supplement: Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
补充:压力和基因组:测试社会效应对基因调控的影响
- 批准号:
9926548 - 财政年份:2017
- 资助金额:
$ 32.08万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
9398561 - 财政年份:2017
- 资助金额:
$ 32.08万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
8717684 - 财政年份:2012
- 资助金额:
$ 32.08万 - 项目类别:
Stress and the Genome: Testing the Impact of Social Effects on Gene Regulation
压力和基因组:测试社会效应对基因调控的影响
- 批准号:
8348248 - 财政年份:2012
- 资助金额:
$ 32.08万 - 项目类别:
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