SSA: Elucidation of epigenomic and transcriptional mechanisms controlling stress-induced Fkbp5 gene expression in the hippocampus

SSA:阐明控制海马应激诱导的 Fkbp5 基因表达的表观基因组和转录机制

基本信息

  • 批准号:
    1942587
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Studentship
  • 财政年份:
    2017
  • 资助国家:
    英国
  • 起止时间:
    2017 至 无数据
  • 项目状态:
    已结题

项目摘要

This PhD studentship is an exciting project to obtain insight into how stress impacts on the brain atthe molecular level. Stress is part of everybody's life. It can become a health problem when a stressfulsituation is extremely traumatic, when exposure to stress becomes chronic, and in cases where thereis an underlying genetic vulnerability. Recently, a genetic vulnerability (a so-called single nucleotidepolymorphism (SNP)) for developing major depression and posttraumatic stress disorder wasdescribed for the gene Fkbp5 (Klengel et al. Nature Neurosci. 2013). The protein product of this gene,Fkbp51, reduces the sensitivity of the glucocorticoid receptor for binding the stress hormones cortisolor corticosterone, glucocorticoid hormones in man and rodents, respectively. Excessive stimulation ofthe glucocorticoid receptor is thought to have detrimental effects on the brain; therefore, Fkbp51plays an important role in keeping glucocorticoid receptor activity within healthy limits. Accordingly,to maintain health and wellbeing appropriate expression of the Fkbp5 gene is of major importance.Presently, however there is only limited information available about how the gene is regulated.Glucocorticoid receptors are known to stimulate expression of the Fkbp5 gene and raise cellular levelsof Fkbp51 protein, thus resulting in reduction of receptor sensitivity to respond to stress hormone.Recently, we discovered that glucocorticoid receptors bind to so-called glucocorticoid-responseelements within the Fkbp5 gene in the hippocampus after stress in vivo (Mifsud & Reul, Proc. Natl.Acad. Sci. USA 2016).The aim of this project is to elucidate how the activity of the Fkbp5 gene is regulated by glucocorticoidreceptors and epigenetic factors like histone modifications and DNA methylation status in vivo. Youwill apply a range of state-of-the-art molecular techniques including chromatin immuno-precipitation(ChIP), quantitative PCR, hnRNA and mRNA analysis and DNA methylation analysis, bioinformaticsanalysis, radioimmunoassays as well as animal experimentation including surgeries. To obtain deeperinsight into the functional properties of particular segments of the Fkbp5 gene in vitro you will use thefront-line gene editing Crispr/Cas9 technology.This project will be supervised by Professor Johannes Reul and Dr Oscar Cordero Llana at the Universityof Bristol and Professor Jonathan Mill at the University of Exeter.
这个博士生项目是一个令人兴奋的项目,以深入了解压力如何在分子水平上影响大脑。压力是每个人生活的一部分。当一个紧张的情况下是非常创伤性的,当暴露于压力成为慢性的,在有潜在的遗传脆弱性的情况下,它可以成为一个健康问题。最近,描述了基因Fkbp 5的发展为重度抑郁症和创伤后应激障碍的遗传易感性(所谓的单核苷酸多态性(SNP))(Kobel等人,Nature Neurosci. 2013年)。该基因的蛋白质产物Fkbp 51降低糖皮质激素受体结合应激激素皮质醇或皮质酮、糖皮质激素的敏感性,分别在人和啮齿动物中。糖皮质激素受体的过度刺激被认为对大脑有不利影响;因此,Fkbp 51在将糖皮质激素受体活性保持在健康范围内方面起着重要作用。因此,为了维持健康和幸福,Fkbp 5基因的适当表达是非常重要的。然而,目前关于该基因如何调节的信息有限。已知糖皮质激素受体刺激Fkbp 5基因的表达并提高Fkbp 51蛋白的细胞水平,从而导致受体对应激激素的敏感性降低。最近,我们发现体内应激后糖皮质激素受体与海马体中Fkbp 5基因内所谓的糖皮质激素反应元件结合(Mifsud & Reul,Proc. Natl. Acad. Sci.该项目的目的是阐明Fkbp 5基因的活性如何受糖皮质激素受体和表观遗传因素如组蛋白修饰和体内DNA甲基化状态的调节。您将应用一系列最先进的分子技术,包括染色质免疫沉淀(ChIP),定量PCR,hnRNA和mRNA分析和DNA甲基化分析,生物信息学分析,放射免疫测定以及包括手术在内的动物实验。为了更深入地了解Fkbp 5基因特定片段的体外功能特性,您将使用一线基因编辑Crispr/Cas9技术。该项目将由布里斯托大学的Johannes Reul教授和Oscar Cordero Llana博士以及埃克塞特大学的Jonathan Mill教授监督。

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 }}

其他文献

Internet-administered, low-intensity cognitive behavioral therapy for parents of children treated for cancer: A feasibility trial (ENGAGE).
针对癌症儿童父母的互联网管理、低强度认知行为疗法:可行性试验 (ENGAGE)。
  • DOI:
    10.1002/cam4.5377
  • 发表时间:
    2023-03
  • 期刊:
  • 影响因子:
    4
  • 作者:
  • 通讯作者:
Differences in child and adolescent exposure to unhealthy food and beverage advertising on television in a self-regulatory environment.
在自我监管的环境中,儿童和青少年在电视上接触不健康食品和饮料广告的情况存在差异。
  • DOI:
    10.1186/s12889-023-15027-w
  • 发表时间:
    2023-03-23
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
  • 通讯作者:
The association between rheumatoid arthritis and reduced estimated cardiorespiratory fitness is mediated by physical symptoms and negative emotions: a cross-sectional study.
类风湿性关节炎与估计心肺健康降低之间的关联是由身体症状和负面情绪介导的:一项横断面研究。
  • DOI:
    10.1007/s10067-023-06584-x
  • 发表时间:
    2023-07
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
  • 通讯作者:
ElasticBLAST: accelerating sequence search via cloud computing.
ElasticBLAST:通过云计算加速序列搜索。
  • DOI:
    10.1186/s12859-023-05245-9
  • 发表时间:
    2023-03-26
  • 期刊:
  • 影响因子:
    3
  • 作者:
  • 通讯作者:
Amplified EQCM-D detection of extracellular vesicles using 2D gold nanostructured arrays fabricated by block copolymer self-assembly.
使用通过嵌段共聚物自组装制造的 2D 金纳米结构阵列放大 EQCM-D 检测细胞外囊泡。
  • DOI:
    10.1039/d2nh00424k
  • 发表时间:
    2023-03-27
  • 期刊:
  • 影响因子:
    9.7
  • 作者:
  • 通讯作者:

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('', 18)}}的其他基金

An implantable biosensor microsystem for real-time measurement of circulating biomarkers
用于实时测量循环生物标志物的植入式生物传感器微系统
  • 批准号:
    2901954
  • 财政年份:
    2028
  • 资助金额:
    --
  • 项目类别:
    Studentship
Exploiting the polysaccharide breakdown capacity of the human gut microbiome to develop environmentally sustainable dishwashing solutions
利用人类肠道微生物群的多糖分解能力来开发环境可持续的洗碗解决方案
  • 批准号:
    2896097
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
A Robot that Swims Through Granular Materials
可以在颗粒材料中游动的机器人
  • 批准号:
    2780268
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Likelihood and impact of severe space weather events on the resilience of nuclear power and safeguards monitoring.
严重空间天气事件对核电和保障监督的恢复力的可能性和影响。
  • 批准号:
    2908918
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Proton, alpha and gamma irradiation assisted stress corrosion cracking: understanding the fuel-stainless steel interface
质子、α 和 γ 辐照辅助应力腐蚀开裂:了解燃料-不锈钢界面
  • 批准号:
    2908693
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Field Assisted Sintering of Nuclear Fuel Simulants
核燃料模拟物的现场辅助烧结
  • 批准号:
    2908917
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Assessment of new fatigue capable titanium alloys for aerospace applications
评估用于航空航天应用的新型抗疲劳钛合金
  • 批准号:
    2879438
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Developing a 3D printed skin model using a Dextran - Collagen hydrogel to analyse the cellular and epigenetic effects of interleukin-17 inhibitors in
使用右旋糖酐-胶原蛋白水凝胶开发 3D 打印皮肤模型,以分析白细胞介素 17 抑制剂的细胞和表观遗传效应
  • 批准号:
    2890513
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
CDT year 1 so TBC in Oct 2024
CDT 第 1 年,预计 2024 年 10 月
  • 批准号:
    2879865
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
  • 批准号:
    2876993
  • 财政年份:
    2027
  • 资助金额:
    --
  • 项目类别:
    Studentship

相似海外基金

Elucidation of mechanism for gross chromosomal rearrangements by genomic and epigenomic studies
通过基因组和表观基因组研究阐明染色体总重排的机制
  • 批准号:
    23K08855
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation of mechanisms of generational toxicology of developmental neurotoxicity - Developmental program and epigenomic toxicity of pesticides
发育神经毒性的代际毒理学机制的阐明 - 农药的发育程序和表观基因组毒性
  • 批准号:
    22H03750
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of human evolutionary process by induction of oogonia from ape iPS cells and their epigenomic analysis
通过猿 iPS 细胞诱导卵原细胞及其表观基因组分析来阐明人类进化过程
  • 批准号:
    21J15117
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Elucidation of the molecular mechanism of epigenomic changes caused by intermittent hypoxia during pregnancy and construction of a foundation for medical applications
阐明妊娠期间间歇性缺氧引起表观基因组变化的分子机制并构建医学应用基础
  • 批准号:
    20H03895
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of the Integrated Epigenomic Control Mechanisms by Metabolic Environment
代谢环境综合表观基因组控制机制的阐明
  • 批准号:
    20H03729
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of transcriptional and epigenomic circuit ro reveal molecular mechanisms underlying heart failure and identify novel therapeutic targets
阐明转录和表观基因组回路,揭示心力衰竭的分子机制并确定新的治疗靶点
  • 批准号:
    20H03673
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Integrative elucidation of lifestyle diseases using the epigenomic memory of kidney cells
利用肾细胞的表观基因组记忆综合阐明生活方式疾病
  • 批准号:
    20K21596
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Elucidation of metabolic mechanisms focusing on genomic abnormalities and epigenomic changes related to tumor-bearing state and drug resistance
阐明与肿瘤荷瘤状态和耐药性相关的基因组异常和表观基因组变化的代谢机制
  • 批准号:
    19K07769
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Elucidation of epigenomic regulation by chromosome segregation factor and identification of novel therapeutic target for leukemia
阐明染色体分离因子的表观基因组调控及白血病新治疗靶点的鉴定
  • 批准号:
    19H03690
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Elucidation of pathogenesis of autoimmune-mediated interstitial lung disease based on epigenomic analysis
基于表观基因组分析阐明自身免疫介导的间质性肺疾病的发病机制
  • 批准号:
    19H03697
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了