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
基本信息
- 批准号:9803109
- 负责人:
- 金额:$ 47.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAfricaAfrican AmericanAmericanAutoimmune DiseasesBacteriaBiological AssayBubonic PlagueCellsCentral AfricaChronicCollectionCommunicable DiseasesComplexDNADataDiseaseEnvironmentEuropeanEvolutionExposure toGene ExpressionGene FrequencyGenesGeneticGenetic DeterminismGenetic MarkersGenetic TranscriptionGenetic VariationGenetic studyGenotypeGrowthHost DefenseHourHumanHuman GenomeImmuneImmune responseImmune systemImmunityImmunologicsImmunologyIndividualInfectionInflammatoryMapsMeasuresMediatingModernizationMolecularNatural SelectionsNorthern AfricaPasteurella pseudotuberculosisPathogenicityPhenotypePlaguePlayPopulationPopulation GeneticsPopulation GroupPredispositionProxyQuantitative Trait LociRecording of previous eventsResistanceResolutionRoleSamplingShapesSingle Nucleotide PolymorphismTechniquesTechnologyTestingTimeVariantWorkYersiniaYersinia infectionsYersinia pestiscytokinefightingfunctional genomicsgenetic variantgenome-widegenome-wide analysishost-pathogen coevolutionhuman genomicsin vitro Assayinduced pluripotent stem cellinfancyinsightmacrophagenovelpandemic diseasepathogenpressureresponseskeletaltooltraittranscriptome sequencing
项目摘要
Project Summary
Pathogens are one of the strongest selective pressures on the human genome. As modern humans
migrated out of Africa, they encountered markedly different pathogenic environments, likely resulting in
population-specific selection of immune phenotypes. Consistent with this hypothesis, some of the most
compelling evidence for local positive selection in the human genome has been detected among genes
involved in immunity and host defense. Yet, our understanding of the role that local adaptation plays in
shaping phenotypic variation in immune responses across populations is still in its infancy. To better
understand the complex relationship between pathogens and host adaptation we propose to study the
selective impact on the immune system of one of the most devastating pathogens in history – Yersinia pestis,
the agent of the Black Death. Since its emergence in Eurasia 1500 to 6400 years ago Y. pestis has swept
Eurasia and North and Central Africa in two major pandemics (Justinian, 541-544; Black Death, starting 1347-
1351) and has subsequently spread nearly worldwide via a third ongoing pandemic. Although Y. pestis is
proposed to have severely culled the Eurasian population, how groups that differ in their historical exposure to
plague respond to the pathogen is not known. Addressing this gap is not only important for understanding the
recent evolution of the human immune system, but may also help reveal the molecular basis of ancestry-
related differences in susceptibility to infectious diseases, chronic inflammatory disorders, and autoimmune
disorders. Using combined expertise in human genomics, immunology, infectious diseases and ancient DNA,
we propose: (i) to characterize inter-individual and inter-population variability in immune responses to infection
with Y. pestis; (ii) to map expression quantitative trait loci (eQTLs) that are associated with variation in
response to infection with Y. pestis; and (iii) to identify genetic loci showing signatures of positive selection by
Y. pestis by looking at “real-time” fluctuations in allele frequencies among immune-related genes and
immunological QTLs sequenced from skeletal remains of European populations living before, during, and after
the Black Death. This work is expected to yield unprecedented insight into the genetic mechanisms associated
with increased protection against Y. pestis as well as reveal novel genetic markers involved in the susceptibility
to and/or protection against contemporary infectious diseases
项目概要
病原体是对人类基因组最强的选择压力之一。作为现代人类
迁出非洲后,他们遇到了明显不同的致病环境,可能导致
免疫表型的人群特异性选择。与这一假设相一致的是,一些最
在基因中检测到人类基因组局部正选择的令人信服的证据
参与免疫和宿主防御。然而,我们对当地适应所发挥的作用的理解
塑造不同人群免疫反应的表型变异仍处于起步阶段。为了更好
了解病原体与宿主适应之间的复杂关系,我们建议研究
历史上最具破坏性的病原体之一——鼠疫耶尔森氏菌对免疫系统的选择性影响,
黑死病的代理人。自从 1500 至 6400 年前在欧亚大陆出现以来,鼠疫耶尔森氏菌已经席卷全球
欧亚大陆以及北非和中非发生了两次重大流行病(查士丁尼,541-544 年;黑死病,始于 1347-
1351),随后通过第三次持续大流行几乎在全世界范围内传播。尽管鼠疫耶尔森氏菌
提议严厉剔除欧亚裔人口,历史上接触不同的群体如何
鼠疫对病原体的反应尚不清楚。解决这一差距不仅对于理解
人类免疫系统的最新进化,但也可能有助于揭示祖先的分子基础
对传染病、慢性炎症性疾病和自身免疫性疾病易感性的相关差异
失调。综合利用人类基因组学、免疫学、传染病和古代 DNA 方面的专业知识,
我们建议:(i)描述个体间和群体间对感染的免疫反应的变异性
鼠疫耶尔森氏菌; (ii) 绘制与变异相关的表达数量性状位点 (eQTL)
对鼠疫耶尔森氏菌感染的反应; (iii) 识别显示正选择特征的遗传位点
鼠疫耶尔森氏菌通过观察免疫相关基因等位基因频率的“实时”波动,
从生活在之前、期间和之后的欧洲人群的骨骼遗骸中测序出的免疫学 QTL
黑死病。这项工作有望对相关遗传机制产生前所未有的见解
增强对鼠疫耶尔森氏菌的保护,并揭示与易感性相关的新遗传标记
和/或预防当代传染病
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 }}
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
{{
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('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:
$ 47.67万 - 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:
$ 47.67万 - 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:
$ 47.67万 - 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:
$ 47.67万 - 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:
$ 47.67万 - 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:
$ 47.67万 - 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:
10204868 - 财政年份:2017
- 资助金额:
$ 47.67万 - 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:
$ 47.67万 - 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:
$ 47.67万 - 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:
$ 47.67万 - 项目类别:
相似海外基金
Multi-component interventions to reducing unhealthy diets and physical inactivity among adolescents and youth in sub-Saharan Africa (Generation H)
采取多方干预措施减少撒哈拉以南非洲青少年的不健康饮食和缺乏身体活动(H 代)
- 批准号:
10106976 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
EU-Funded
Exploring the mental health and wellbeing of adolescent parent families affected by HIV in South Africa
探讨南非受艾滋病毒影响的青少年父母家庭的心理健康和福祉
- 批准号:
ES/Y00860X/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Fellowship
Decolonization, Appropriation and the Materials of Literature in Africa and its Diaspora
非洲及其侨民的非殖民化、挪用和文学材料
- 批准号:
EP/Y024516/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Research Grant
Exploring "Actionable Information" for Learning Improvement in Rural East Africa: A Positive Deviance Approach
探索东非农村地区学习改进的“可行信息”:积极偏差方法
- 批准号:
24K00390 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
ePowerCart - Affordable Mobile Clean Energy for Remote Communities in Rural Sub-Saharan Africa and India
ePowerCart - 为撒哈拉以南非洲和印度农村偏远社区提供经济实惠的移动清洁能源
- 批准号:
10076185 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Collaborative R&D
Protecting Women from Economic shocks to fight HIV in Africa (POWER)
保护非洲妇女免受经济冲击,抗击艾滋病毒 (POWER)
- 批准号:
MR/Y003837/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Fellowship
Tackling antimicrobial resistance across dentistry in Sub-Saharan Africa.
解决撒哈拉以南非洲牙科领域的抗菌素耐药性问题。
- 批准号:
MR/Y019695/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Research Grant
Water stressed cities: individual choice, access to water and pathways to resilience in sub-Saharan Africa
缺水城市:撒哈拉以南非洲地区的个人选择、水资源获取和恢复力途径
- 批准号:
MR/X022943/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Fellowship
The Open fracture National Evaluation (ONE) Study - South Africa: Improving outcomes in the care of open fractures in low resource settings
开放性骨折国家评估 (ONE) 研究 - 南非:改善资源匮乏地区开放性骨折的护理效果
- 批准号:
MR/Y00955X/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Fellowship
Recognising & supporting informal mhealth in Africa through grassroots interventions (REIMAGINE)
认识
- 批准号:
MR/Y015614/1 - 财政年份:2024
- 资助金额:
$ 47.67万 - 项目类别:
Research Grant














{{item.name}}会员




