Epigenetic and metabolic mechanisms of environmentally-induced transgenerational germline dysfunction
环境诱导的跨代种系功能障碍的表观遗传和代谢机制
基本信息
- 批准号:10606928
- 负责人:
- 金额:$ 34.36万
- 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:2023-06-01 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:Acetate-CoA LigaseAcetatesAcetyl Coenzyme AAcetylationAddressAlcohol consumptionAlcoholsApoptosisAutomobile DrivingBindingBiological ModelsBrainCaenorhabditis elegansChildChromatinChromosome PairingComplexCytologyDataDefectDiseaseDrosophila genusEmbryoEnvironmentEnvironmental ExposureEnvironmental ImpactEpigenetic ProcessEthanolEthanol MetabolismEventExposure toFetal Alcohol ExposureFetal Alcohol SyndromeFoundationsFunctional disorderFuture GenerationsGenerationsGeneticGenetic RecombinationGenomeGerm CellsGoalsHeritabilityHistone AcetylationHistonesHumanIncidenceKnowledgeLinkMammalsMapsMass Spectrum AnalysisMediatorMeiosisMemoryMetabolicMetabolic PathwayModelingModificationMolecularMorphologyMusNematodaNeurologicNuclearOrganismOutcomePathway interactionsPhysiologicalPost-Translational Protein ProcessingPregnancyRattusRegulationReportingReproductionReproductive HistoryResearchRodent ModelSeminalSymptomsTestingTissuesWestern EuropeWomanWorkalcohol effectalcohol exposurealcohol responsealcohol testingbehavioral impairmentdesignepigenomeepigenomicsfetalhistone modificationhomologous recombinationmodel organismneurobehavioralpharmacologicpreferenceprenatal exposureprogramsreproductivereproductive functionreproductive outcomestemtooltransgenerational epigenetic inheritancetransmission process
项目摘要
PROJECT SUMMARY
The overarching goal of the research presented in this application is to dissect the genetic, epigenetic, and
metabolic programs that encode and transmit a memory of environmental exposure for several generations. In
that context, we aim to understand how environmental influences alter the reproductive program of organisms
in a transgenerational fashion and what makes the germline a particularly important and sensitive target of
exposures.
In mammals, in utero ethanol exposure is associated with an array of well-characterized morphological,
neurobehavioral, and reproductive issues. However, there is mounting evidence in a variety of model
organisms that some adverse reproductive and neurological features are also detectable in the third generation
following exposure indicating a transgenerational effect. Alcohol also has a clear epigenetic impact and directly
contributes to the modification of the epigenome. Nevertheless, despite the fact that heritable effects of alcohol
imply an alteration of the information contained in germ cells, it is unclear how the memory of ethanol exposure
is initiated in the germline and then transmitted to future generations. Here, we combine the tractability and
conservation of the model system C. elegans with state-of-the-art epigenomic analyses, classical genetic, and
cytological approaches to shed light on the mechanisms of memory of ethanol exposure. Our preliminary data
shows that ethanol exposure causes strong transgenerational reproductive and behavioral impairments. We
also show that, in line with recent mammalian studies, ethanol causes an increase in histone acetylation.
Thus, we hypothesize that ethanol exposure causes transgenerational perturbations of germline
function by altering the germline epigenome, specifically histone acetylation. Our aims are designed to
address the molecular, metabolic and epigenetic requirements for these transgenerational impacts of ethanol.
In aim 1, we will build on our preliminary reproduction data to interrogate through classical genetics tools
meiotic pathways at the root of ethanol's trans-generational increase in germline apoptosis and embryonic
lethality. In aim 2, we will examine via mass spectrometry the modulation in 80 different histone marks
stemming from direct ethanol exposure and test whether increased histone acetylation is a required event for
the initiation ethanol's transgenerational reproductive effects. Finally, in aim 3, we will test the epigenetic
requirement for the transgenerational transmission of ethanol's effects and also map by CUT&RUN the
changes in the epigenetic landscape of histone modifications in the germline.
At the completion of the aims, we will have identified the molecular underpinnings for the initiation and
transmission of ethanol transgenerational reproductive outcomes.
项目总结
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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Patrick Allard其他文献
Patrick Allard的其他文献
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{{ truncateString('Patrick Allard', 18)}}的其他基金
Role of epigenetic crosstalks in directing locus sensitivity to arsenic
表观遗传串扰在引导基因座对砷的敏感性中的作用
- 批准号:
10608433 - 财政年份:2023
- 资助金额:
$ 34.36万 - 项目类别:
E-Cigarette Vaping during Pregnancy and Lactation, Germ Cell Epigenetic Memory, and Transgenerational Asthma
怀孕和哺乳期电子烟、生殖细胞表观遗传记忆和跨代哮喘
- 批准号:
10428619 - 财政年份:2020
- 资助金额:
$ 34.36万 - 项目类别:
E-Cigarette Vaping during Pregnancy and Lactation, Germ Cell Epigenetic Memory, and Transgenerational Asthma
怀孕和哺乳期电子烟、生殖细胞表观遗传记忆和跨代哮喘
- 批准号:
10657604 - 财政年份:2020
- 资助金额:
$ 34.36万 - 项目类别:
Mechanisms of environmental epigenetic disruption and memory of exposure in germ cells
环境表观遗传破坏机制和生殖细胞暴露记忆
- 批准号:
10112905 - 财政年份:2017
- 资助金额:
$ 34.36万 - 项目类别:
Germ Cell-Mediated Epigenetic Memory of Ethanol Exposure
生殖细胞介导的乙醇暴露表观遗传记忆
- 批准号:
9235656 - 财政年份:2017
- 资助金额:
$ 34.36万 - 项目类别:
Mechanisms of environmental epigenetic disruption and memory of exposure in germ cells
环境表观遗传破坏机制和生殖细胞暴露记忆
- 批准号:
9217336 - 财政年份:2017
- 资助金额:
$ 34.36万 - 项目类别:
Student-to-Scientist Bridge Program in Environmental Health Science (S2S Bridge)
环境健康科学学生与科学家的桥梁计划(S2S Bridge)
- 批准号:
9044779 - 财政年份:2015
- 资助金额:
$ 34.36万 - 项目类别:
Student-to-Scientist Bridge Program in Environmental Health Science (S2S Bridge)
环境健康科学学生与科学家的桥梁计划(S2S Bridge)
- 批准号:
9247182 - 财政年份:2015
- 资助金额:
$ 34.36万 - 项目类别:
Design of a high-throughput screen for chemicals that cause meiotic aneuploidy
导致减数分裂非整倍体化学物质的高通量筛选设计
- 批准号:
8586524 - 财政年份:2012
- 资助金额:
$ 34.36万 - 项目类别:
Design of a high-throughput screen for chemicals that cause meiotic aneuploidy
导致减数分裂非整倍体化学物质的高通量筛选设计
- 批准号:
8775669 - 财政年份:2012
- 资助金额:
$ 34.36万 - 项目类别:
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