Linking genomic, physiological, and behavioral responses using a Drosophila model of heavy metal stress
使用重金属应激的果蝇模型将基因组、生理和行为反应联系起来
基本信息
- 批准号:10283505
- 负责人:
- 金额:$ 9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAllelesBar CodesBehaviorBehavioralBehavioral GeneticsBiological AssayBiological ModelsCadmiumCandidate Disease GeneCessation of lifeChromosome MappingCommunitiesComplexCopperCoupledDNA ResequencingDataDecision MakingDesire for foodDetectionDevelopmentDiseaseDrosophila genusDrosophila melanogasterEnvironmental HealthEvolutionExposure toGene ExpressionGene FrequencyGenerationsGenesGeneticGenetic ModelsGenetic RiskGenetic VariationGenomicsHealthHeavy MetalsHumanInfrastructureInvestigationLeadLearningLearning DisabilitiesLifeLinkManganeseMeasuresMemoryMetal exposureMetalsModelingMorbidity - disease rateNatural ResistanceNervous System PhysiologyNeurologicOrganismPathologyPathway interactionsPhasePhenotypePhysiologicalPhysiologyPollutionPopulationPovertyPredispositionProcessQuantitative Trait LociRNARecording of previous eventsResearchResistanceResourcesRiskStressSyndromeSystemTestingTimeToxic effectValidationVariantWhole OrganismWorkZincacute toxicitybehavior influencebehavioral genomicsbehavioral responsecopper poisoningdisabilityendophenotypeenvironmental stressorexperimental studyflygene environment interactiongene expression variationgenetic architecturegenetic risk factorgenetic variantgenome sequencinghuman diseaseinnovationinsightinterestlarge datasetslife historylow socioeconomic statusmetal metabolismmetal poisoningneglectnervous system disordernovelpollutantpreferencepressureracial disparityresponsestressortooltraittranscriptome sequencingwhole genome
项目摘要
Contact PD/PI: Everman, Elizabeth
PROJECT SUMMARY
Heavy metal pollution has pervasive environmental, health, and evolutionary impacts. In humans, health risks of
heavy metals ranging from permanent neurological disease to increased morbidity of degenerative syndromes
are exacerbated by poverty and fragile community infrastructure. Physiological responses to heavy metals
including lead, cadmium, and copper have complex genetic architectures, and several heavy metals are known
to hinder learning and alter behavior. However, these behavioral and physiological responses to metal stress
are often considered in isolation, neglecting the specific genetic relationship between metal toxicity and
behavioral response to metal stress. My primary objective is to dissect and characterize this whole organism
heavy metal response by taking an integrative approach to examine the genetic basis of the relationship between
physiological, behavioral, and evolutionary responses to heavy metal stress. The elite genetic model Drosophila
melanogaster is ideal for my research because it shares many heavy metal-responsive genes with humans, it is
extremely facile to conduct large-scale phenotyping assays, and an enormous plethora of sophisticated tools
are available to facilitate in-depth behavioral and genomic experiments. I treat copper as my model heavy metal
because, although required at low levels for normal development and physiological function, it is a common
heavy metal pollutant that is metabolized and bioaccumulated by genes that also interact with lead, manganese,
zinc, and cadmium. With Aim 1, I will disentangle the genetic link between physiological and behavioral
responses to copper stress using a large mapping panel of genetically stable strains and combining large-scale
screens of multiple behavioral traits with physiological data collected across multiple life stages. With Aim 2, I
will characterize genetic and coevolutionary responses to copper selection in multiple populations derived from
high and low copper resistance natural populations. Aim 2 will involve an evolve and resequencing (E&R)
approach coupled with bulk RNA barcoding and sequencing (BRB-seq) to track the dynamic shifts in allele
frequencies and gene expression through the course of artificial selection for copper resistance. Investigation of
the evolutionary processes that lead to complex trait variation has great biomedical significance as we seek to
understand the gene-by-environment interactions, genetic constraints, and genetic risk factors that contribute to
increased susceptibility to toxic heavy metal exposure in human populations. This integrative approach leverages
QTL mapping, whole genome and RNA-seq, sophisticated functional validation tools available for the D.
melanogaster model system, and experimental evolution. This work will ultimately allow for the characterization
of genetic variation in chemosensory ability, traits related to decision making, and neurological function in
response to copper stress in diverse synthetic and naturally derived genetic backgrounds. Together, these
approaches will provide critical insight into the interconnectedness of multiple response traits, while also
illuminating genetic factors that influence behavioral and learning disabilities linked to metal poisoning.
联系PD/PI:Everman,Elizabeth
项目摘要
重金属污染具有广泛的环境、健康和进化影响。在人类中,
重金属从永久性神经系统疾病到退行性综合征发病率增加
贫困和脆弱的社区基础设施加剧了这一问题。重金属胁迫的生理反应
包括铅、镉和铜都有复杂的遗传结构,
阻碍学习和改变行为。然而,这些对金属压力的行为和生理反应
通常被孤立地考虑,忽略了金属毒性和
对金属应激的行为反应我的主要目标是解剖和描述整个有机体
重金属的反应,采取综合的方法来研究遗传基础的关系,
生理、行为和进化对重金属胁迫的反应。精英遗传模型果蝇
黑腹果蝇是我研究的理想对象,因为它与人类有许多重金属反应基因,
非常容易进行大规模的表型分析,以及大量复杂的工具
可用于促进深入的行为和基因组实验。我把铜当作我的重金属模型
因为,尽管正常发育和生理功能所需的水平较低,但它是一种常见的
重金属污染物通过基因代谢和生物积累,这些基因也与铅、锰
锌和镉。通过目标1,我将解开生理和行为之间的遗传联系
使用遗传稳定菌株的大型绘图面板并结合大规模的
通过在多个生命阶段收集的生理数据筛选多种行为特征。目标2,我
将描述遗传和共同进化的反应,铜选择在多个群体来自
高和低铜抗性自然种群。目标2将涉及进化和重新排序(E&R)
与批量RNA条形码化和测序(BRB-seq)相结合的方法来跟踪等位基因的动态变化
通过铜抗性人工选择过程中的频率和基因表达。调查
导致复杂性状变异的进化过程具有重大的生物医学意义,因为我们试图
了解基因与环境的相互作用,遗传限制和遗传风险因素,有助于
人类对有毒重金属暴露的易感性增加。这种综合方法利用了
QTL定位、全基因组和RNA-seq等成熟的功能验证工具可用于D.
黑胃模型系统和实验进化。这项工作将最终允许表征
化学感受能力的遗传变异,与决策有关的特征,以及神经功能,
在不同的合成和自然衍生的遗传背景中对铜胁迫的反应。所有这些
方法将提供关键的洞察力的相互联系,多种反应特质,同时也
阐明影响与金属中毒有关的行为和学习障碍的遗传因素。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Elizabeth Everman的其他文献
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{{ truncateString('Elizabeth Everman', 18)}}的其他基金
Linking genomic, physiological, and behavioral responses using a Drosophila model of heavy metal stress
使用重金属应激的果蝇模型将基因组、生理和行为反应联系起来
- 批准号:
10842536 - 财政年份:2023
- 资助金额:
$ 9万 - 项目类别:
Linking genomic, physiological, and behavioral responses using a Drosophila model of heavy metal stress
使用重金属应激的果蝇模型将基因组、生理和行为反应联系起来
- 批准号:
10462755 - 财政年份:2021
- 资助金额:
$ 9万 - 项目类别:
Genetic dissection and characterization of variation in copper resistance in Drosophila melanogaster
果蝇铜抗性变异的遗传解剖和表征
- 批准号:
9980699 - 财政年份:2019
- 资助金额:
$ 9万 - 项目类别:
Genetic dissection and characterization of variation in copper resistance in Drosophila melanogaster
果蝇铜抗性变异的遗传解剖和表征
- 批准号:
9761196 - 财政年份:2019
- 资助金额:
$ 9万 - 项目类别:
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