Rates of histone turnover and functional significance in fetal alcohol syndrome
胎儿酒精综合征中的组蛋白周转率和功能意义
基本信息
- 批准号:9315673
- 负责人:
- 金额:$ 18.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcetaldehydeAddressAdverse effectsAffectAlcoholsAmygdaloid structureAnimalsApoptosisAreaBehavioralBiological MarkersBrainBrain InjuriesBrain regionBrain-Derived Neurotrophic FactorCell CycleCell DeathCell SurvivalCellsCentral Nervous System DiseasesCerebellumCerebral cortexCerebrumCharacteristicsChildCodeCognitive deficitsComplexCorpus CallosumCoupledCytoplasmic GranulesDNADNA DamageDNA MethylationDNA Repair DisorderDNA Repair GeneDefectDeuterium OxideDevelopmentDiagnosisDiseaseDysmorphologyEpigenetic ProcessEthanolEthanol MetabolismFaceFetal Alcohol ExposureFetal Alcohol Spectrum DisorderFetal Alcohol SyndromeFetal DevelopmentFetusFiberGene ExpressionGene Expression RegulationGene ProteinsGene-ModifiedGenesGenomic InstabilityGrowthHalf-LifeHippocampus (Brain)HistonesHumanHypothalamic structureIndividualInvestigationKineticsLabelLeadLocationMass Spectrum AnalysisMeasurementMeasuresMediatingMediator of activation proteinMental HealthMethodsMicrocephalyModelingMolecularNeurogliaNeuronsPathologyPathway interactionsPhenotypePhysiologicalPost-Translational Protein ProcessingPrefrontal CortexProductionProtein BiosynthesisProtein IsoformsProteinsProteomeProteomicsPublic HealthRadialRattusReactive Oxygen SpeciesResearch PersonnelResolutionRoleSocial AdjustmentStable Isotope LabelingStructural defectStudy modelsTechniquesTeratogenic effectsThalamic structureTherapeutic InterventionThird Pregnancy TrimesterTimeTissuesTracerVariantWorkadverse outcomealcohol consumption during pregnancyalcohol effectalcohol exposurealcohol preventionbasebeta-Endorphinbiomarker discoverybrain sizecell growthcritical developmental periodcritical periodepigenetic regulationepigenomefetalhistone modificationimprovedin vivoinnovationlaser capture microdissectionneurobehavioralneurogenesisneuron lossneuroproteomicsneurotoxicnovelpostnatalprenatalprenatal exposureprotein degradationprotein expressionpublic health relevanceresponsesocial stressstable isotopestress tolerancetool
项目摘要
DESCRIPTION (provided by applicant): Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). These disorders range from growth retardation to neurobehavioral alterations including mental health problems, poor social adjustment and poor stress tolerance. Fetal alcohol defects range from diminution in the size of the brain region to microstructural pathology at the level of loss of neurons and glial cells, ectopic locations of neurons and glia, or defects in fiber tracts. The neurotoxic actions of ethanol during development reduce the number of hippocampal neurons, cortical neurons, cerebral granule and Purkinje neurons and hypothalamic neurons. Our work and that of others have shown that alcohol metabolism releases bi-products, such as acetaldehyde and reactive oxygen species (ROS), which can cause DNA damage and in conditions of DNA repair deficiencies can lead to genomic instability and cell death. Recent investigation of possible epigenetic mechanisms involving DNA methylation and histone modifications as mediators of alcohol's adverse effects on the brain of the fetus provides a promising approach for understanding the complex observable characteristics associated with FAS. Unfortunately, to this point, all of the methods that have been used to study epigenetic modifications of genes causing many fetal alcohol syndrome phenotypes rely on static measurements. We believe that quantifying histone turnover might be an important parameter that can contribute to better understanding of epigenetic regulation of gene expression in developing brain. Our central hypothesis is that histone turnover might be an important parameter that can contribute to the ethanol-mediated epigenetic alterations leading to defects in gene expression and cell survival. We propose to use a novel stable isotope tracer method that we recently developed, which enables measurements of protein synthesis and turnover in vivo, to answer this question. The studies outlined in this proposal will couple standard proteomic analyses with our kinetic method using heavy water labeling and LC-MS/MS to simultaneously measure the half-life and abundance of core histones, histone variants and their post-translationally modified isoforms and determine the functional significance of histone turnover on gene expression and protein network, with specific emphasis on DNA damage response pathways. The proposed studies are highly innovative as they would be the first to characterize histone kinetics in the developing brain, they may also identify new areas for therapeutic intervention as well as markers for fetal alcohol spectrum disorders.
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 }}
NADIA RACHDAOUI其他文献
NADIA RACHDAOUI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 }}
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 18.41万 - 项目类别:
Research Grant