Toxicogenomics of metal response in genetically-variable Drosophilapopulations

遗传变异果蝇种群中金属反应的毒理学

基本信息

  • 批准号:
    10088445
  • 负责人:
  • 金额:
    $ 20.45万
  • 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:
    2019-02-01 至 2023-09-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Environmental toxins present considerable risk to human health, and among the most concerning are toxic metals. Due to broad industrial use and historically widespread incorporation into common products (e.g., paints), there is widespread metal contamination of drinking water, food items, and soil. Even extremely low levels of exposure to certain metals can have deleterious consequences for human health. This is especially true for children since metal exposure has been associated with poorer cognitive function and neurological problems. Given the major health risks associated with metal toxicity it is critical to understand the genetic, epigenetic, and molecular pathways underlying the response to toxic metals. It is clear there is considerable variation among individuals in how they respond to a given toxic compound, whether it is an environmental metal toxin such as lead, or a pharmaceutical compound such as a chemotherapeutic. For some individuals a particular dose can be highly damaging, while for others that same dose has a much more minor effect. Understanding the nature of differential response to a toxic metal challenge, and finding genes that contribute to variation in susceptibility to metal toxicity, will enable us to more accurately predict the risks associated with exposure, better understand the symptoms associated with metal toxicity, and more specifically treat exposed individuals. A principal challenge with exploring genetic variation for metal toxicity response directly in humans is the extreme toxicity of the metals, precluding ethical human studies, and the lack of control of toxin dose in any population-based study. Considerable advantages are offered by model laboratory systems such as Drosophila (fruitflies); Exposure levels can be precisely controlled, tissue-specific measures of gene expression can be gathered, and candidate toxicity genes can be functionally validated using a sophisticated genetic toolkit. Critically, there is broad conservation between humans and flies, including many genes involved in brain development and neuronal function, and many known metal response and detoxification genes. Thus, studies in flies can provide fundamental insight into toxicity variation in human populations. In this proposal we will exploit a very large, genetically well-characterized panel of Drosophila inbred lines. We will integrate data from powerful, efficient toxicity screens, and from a series of sophisticated genomics studies that generate genomewide gene expression measures and maps of regulatory regions. As a result, we will identify mechanisms and genes contributing to variation in toxicity to four key environmental and industrial metal toxins; lead, mercury, cadmium, and manganese.
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)

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 }}

Stuart John Macdonald其他文献

Stuart John Macdonald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('Stuart John Macdonald', 18)}}的其他基金

A Genomic Analysis of Sexual Trait Variation Within and Between Species
物种内和物种间性特征变异的基因组分析
  • 批准号:
    7987493
  • 财政年份:
    2010
  • 资助金额:
    $ 20.45万
  • 项目类别:
A Genomic Analysis of Sexual Trait Variation Within and Between Species
物种内和物种间性特征变异的基因组分析
  • 批准号:
    8492113
  • 财政年份:
    2010
  • 资助金额:
    $ 20.45万
  • 项目类别:
A Genomic Analysis of Sexual Trait Variation Within and Between Species
物种内和物种间性特征变异的基因组分析
  • 批准号:
    8290586
  • 财政年份:
    2010
  • 资助金额:
    $ 20.45万
  • 项目类别:
A Genomic Analysis of Sexual Trait Variation Within and Between Species
物种内和物种间性特征变异的基因组分析
  • 批准号:
    8101303
  • 财政年份:
    2010
  • 资助金额:
    $ 20.45万
  • 项目类别:
A resource for the genetic analysis of complex traits
复杂性状遗传分析的资源
  • 批准号:
    7893982
  • 财政年份:
    2009
  • 资助金额:
    $ 20.45万
  • 项目类别:
A resource for the genetic analysis of complex traits
复杂性状遗传分析的资源
  • 批准号:
    7533713
  • 财政年份:
    2008
  • 资助金额:
    $ 20.45万
  • 项目类别:
A resource for the genetic analysis of complex traits
复杂性状遗传分析的资源
  • 批准号:
    8068749
  • 财政年份:
    2008
  • 资助金额:
    $ 20.45万
  • 项目类别:
A resource for the genetic analysis of complex traits
复杂性状遗传分析的资源
  • 批准号:
    8255484
  • 财政年份:
    2008
  • 资助金额:
    $ 20.45万
  • 项目类别:
A resource for the genetic analysis of complex traits
复杂性状遗传分析的资源
  • 批准号:
    7651425
  • 财政年份:
    2008
  • 资助金额:
    $ 20.45万
  • 项目类别:

相似海外基金

Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
  • 批准号:
    502556
  • 财政年份:
    2024
  • 资助金额:
    $ 20.45万
  • 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
  • 批准号:
    10659303
  • 财政年份:
    2023
  • 资助金额:
    $ 20.45万
  • 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
  • 批准号:
    10674405
  • 财政年份:
    2023
  • 资助金额:
    $ 20.45万
  • 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
  • 批准号:
    10758772
  • 财政年份:
    2023
  • 资助金额:
    $ 20.45万
  • 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
  • 批准号:
    10676499
  • 财政年份:
    2023
  • 资助金额:
    $ 20.45万
  • 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
  • 批准号:
    2748611
  • 财政年份:
    2022
  • 资助金额:
    $ 20.45万
  • 项目类别:
    Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
  • 批准号:
    10532032
  • 财政年份:
    2022
  • 资助金额:
    $ 20.45万
  • 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
  • 批准号:
    22K05630
  • 财政年份:
    2022
  • 资助金额:
    $ 20.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
  • 批准号:
    10525070
  • 财政年份:
    2022
  • 资助金额:
    $ 20.45万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10689017
  • 财政年份:
    2022
  • 资助金额:
    $ 20.45万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了