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.
项目摘要
社会环境对人类的健康和福祉有着明显而深刻的影响。慢性社交
压力和获得社会支助的机会减少与主要的老龄化疾病密切相关;因此,
逆境对预期寿命本身有很强的预测性。最近的证据表明,虽然其中一些
相关因素如吸烟、肥胖和医疗保健的获得、社会
应激源也对生理功能有直接影响。事实上,动物模型的研究显然
研究表明,仅仅是社会从属关系的经历就可以改变免疫系统的功能,
一部分是通过改变免疫细胞中的基因调节。
拟议研究的目标是解决从这些发现中产生的一个关键的悬而未决的问题:
慢性社会压力对免疫功能的影响在什么时候、对谁最重要?为此,
雌性恒河猴优势等级作为慢性社会应激暴露的模型
人类雌性恒河猴是人类社会压力的绝佳模型,因为它们天生
组织成统治等级等级,其中低等级的个体经历增加的比率,
骚扰,减少社会联系,以及与等级相关的压力的生理标志。重要的是,
优势等级分配,因此,一个人的暴露于社会压力,可以操纵在这一点上,
通过操纵群体成员来控制物种。这样的操作产生了一个强大的实验模型,
调查社会引发的压力的后果--一种直接适用于人类的方法,
但这在人类身上是不可能的
拟议的研究将利用这一模型来探讨差异暴露于优势如何
等级引起的社会压力会影响免疫系统中的基因表达。具体来说,它将使用
一种有效筛选条件特异性社会应激对基因表达水平影响的体外方法
跨越30种生理相关的环境条件(例如,病原体暴露,类固醇激素
信令)。它将补充体外筛选与基因调控和抗体的体内测试
对流感疫苗接种的反应,一种特别关注可变反应的医疗程序
随着个人年龄的增长。最后,它将测试年龄,社会行为和基因型是否可以用来预测
社会压力对免疫调节的影响强度的个体间差异,因此,
个人最脆弱。总之,拟议的分析将提供急需的洞察力,
解释个体何时以及为何对相同社会压力源的反应不同的因素,以及
这些差异对医疗的潜在影响。因此,该项目的成果将
直接翻译应用,以确定我们老龄化人口中最易感的成员,
提出了量身定制的干预策略。
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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