Genomic and Physiological Impact of Transposable Elements.

转座元件的基因组和生理影响。

基本信息

  • 批准号:
    10623912
  • 负责人:
  • 金额:
    $ 62.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-08 至 2028-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Transposable Elements (TEs) make up a large fraction of vertebrate genomes, including half of the human genome. The mutagenic properties of TEs are well documented and they are important drivers of genetic variation between and within species. However, how this enormous source of genetic variation has shaped the evolution and biology of species remains poorly understood. Our MIRA project is designed to yield transformative insights into the biological significance of TEs in evolution and disease. Our previous research has focused on the long-term impact of vertebrate TEs in driving genetic innovations. Notably, we showed that TEs have been a recurrent source of raw sequence material co- opted during vertebrate evolution to create new cis-regulatory elements driving changes in gene expression and new protein-coding genes underlying the emergence of novel cellular functions. Most of these events involved ancient TEs long inactive transpositionally. In this next funding cycle, we are turning our attention to young TEs -- those recently or currently mobile. We focus on the developmental impact of young TEs in humans and in zebrafish, a powerful model organism for studies of vertebrate development. By focusing on the functional impact of young retroelements in embryonic development we will uncover the molecular underpinnings of evolutionarily recent biological innovations. Notably, we will investigate the regulatory contribution of TEs in defining features of the human placenta, such as its deep invasion into maternal decidual tissue, and the functional significance of endogenous viral-like particles produced in the early stages of human embryonic development. Our work will also uncover general principles that lead to the cooption of specific TE sequences for cellular function. Specifically, we will test a new provocative model of host-TE interaction in which organismal development becomes dependent on TE- encoded products. We will test this ‘addiction model’ by studying the trans-regulatory activities of Gag (capsid) proteins encoded by endogenous retroviruses in human and zebrafish for which we have obtained preliminary evidence they modulate embryonic developmental processes. The outcomes of this project are expected to shift our view of host-TE interactions from conflicting to mutualistic. Our studies will also yield new mechanistic insights into poorly understood disease processes, such as pregnancy loss by preeclampsia and neurodevelopmental disorders, implicating the dysregulation of young TEs.
项目摘要 转座因子(Transposable Elements,TE)构成脊椎动物基因组的很大一部分,包括脊椎动物基因组的一半。 人类基因组TE的致突变特性已被充分记录,并且它们是致突变的重要驱动因素。 物种间和物种内的遗传变异。然而,这种巨大的遗传变异来源 对物种的进化和生物学仍知之甚少。我们的MIRA项目是 旨在对TE在进化和疾病中的生物学意义产生变革性的见解。 我们以前的研究主要集中在脊椎动物TE在驱动遗传过程中的长期影响上。 创新。值得注意的是,我们发现TE一直是原始序列材料的重复来源, 在脊椎动物进化过程中选择创造新的顺式调节元件, 表达和新的蛋白质编码基因的基础上出现的新的细胞功能。大部分 这些事件涉及古老的TE长期不活跃的换位。在下一个融资周期,我们将 我们对年轻的技术工程师的关注--那些最近或正在移动的。我们专注于发展影响 人类和斑马鱼中年轻的TE,这是脊椎动物研究的一个强大的模式生物 发展通过关注胚胎发育过程中年轻的逆转录因子的功能影响, 将揭示最近生物学创新的分子基础。值得注意的是,我们将 研究TE在定义人类胎盘特征方面的调节作用,例如其深 侵入母体蜕膜组织,以及内源性病毒样颗粒的功能意义 在人类胚胎发育的早期阶段产生。我们的工作还将揭示一般原则 导致细胞功能的特定TE序列的协同选择。具体来说,我们将测试一种新的 宿主-TE相互作用的挑衅性模型,其中生物体发育变得依赖于TE- 编码产品。我们将通过研究Gag(衣壳)的反式调节活动来测试这种“成瘾模型” 在人类和斑马鱼内源性逆转录病毒编码的蛋白质,我们已经获得了初步的 它们调节胚胎发育过程的证据。预计该项目的成果将 将我们对宿主-TE相互作用的观点从冲突转变为互利。我们的研究还将产生新的机制 对疾病过程知之甚少的见解,如先兆子痫导致的妊娠丢失, 神经发育障碍,涉及年轻TE的失调。

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 }}

Cedric Feschotte其他文献

Cedric Feschotte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('Cedric Feschotte', 18)}}的其他基金

Genomic and physiological impact of transposable elements
转座元件的基因组和生理影响
  • 批准号:
    10238949
  • 财政年份:
    2017
  • 资助金额:
    $ 62.73万
  • 项目类别:
Endogenous retroviruses co-opted for immune defenses
内源性逆转录病毒选择免疫防御
  • 批准号:
    9107893
  • 财政年份:
    2015
  • 资助金额:
    $ 62.73万
  • 项目类别:
DNA transposons: evolutionary history and genomic impact in vertebrates
DNA 转座子:脊椎动物的进化史和基因组影响
  • 批准号:
    8297913
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
Human DNA transposons: evolutionary history and genomic impact
人类 DNA 转座子:进化史和基因组影响
  • 批准号:
    7569023
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
Human DNA transposons: evolutionary history and genomic impact
人类 DNA 转座子:进化史和基因组影响
  • 批准号:
    7760194
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
DNA transposons: evolutionary history and genomic impact in vertebrates
DNA 转座子:脊椎动物的进化史和基因组影响
  • 批准号:
    8515452
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
Human DNA transposons: evolutionary history and genomic impact
人类 DNA 转座子:进化史和基因组影响
  • 批准号:
    8018679
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
Human DNA transposons: evolutionary history and genomic impact
人类 DNA 转座子:进化史和基因组影响
  • 批准号:
    7193036
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
DNA transposons: evolutionary history and genomic impact in vertebrates
DNA 转座子:脊椎动物的进化史和基因组影响
  • 批准号:
    8897381
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:
DNA transposons: evolutionary history and genomic impact in vertebrates
DNA 转座子:脊椎动物的进化史和基因组影响
  • 批准号:
    8726422
  • 财政年份:
    2007
  • 资助金额:
    $ 62.73万
  • 项目类别:

相似海外基金

Establishment of a method for evaluating automobile driving ability focusing on frontal lobe functions and its application to accident prediction
以额叶功能为中心的汽车驾驶能力评价方法的建立及其在事故预测中的应用
  • 批准号:
    20K07947
  • 财政年份:
    2020
  • 资助金额:
    $ 62.73万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Evaluation of the Effectiveness of Multi-Professional Collaborative Assessment of Cognitive Function and Automobile Driving Skills and Comprehensive Support
认知功能与汽车驾驶技能多专业协同评估效果评价及综合支持
  • 批准号:
    17K19824
  • 财政年份:
    2017
  • 资助金额:
    $ 62.73万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Development of Flexible Automobile Driving Interface for Disabled People
残疾人灵活汽车驾驶界面开发
  • 批准号:
    25330237
  • 财政年份:
    2013
  • 资助金额:
    $ 62.73万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Automobile driving among older people with dementia: the effect of an intervention using a support manual for family caregivers
患有痴呆症的老年人的汽车驾驶:使用家庭护理人员支持手册进行干预的效果
  • 批准号:
    23591741
  • 财政年份:
    2011
  • 资助金额:
    $ 62.73万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了