Engineering and Imaging 3D genome structure-function dynamics across time scales

工程与成像 跨时间尺度的 3D 基因组结构-功能动态

基本信息

  • 批准号:
    10264929
  • 负责人:
  • 金额:
    $ 112.83万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-16 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

The mammalian genome folds into tens of thousands of long-range looping interactions. A critical unknown is whether and how chromatin loops control gene expression, and a major unresolved question is how the temporal progression of loops relates to transcription dynamics. One major barrier to answering this question is that loops change on a range of timescales, necessitating the use of tools and model systems amenable to tracking and engineering loops longitudinally and in real time on both short and long timing. Here, we propose to develop and apply new engineering and imaging tools to measure, induce, and perturb loops with precise temporal control in three different biological systems spanning minutes, hours, and weeks. At the shortest timescale (minutes, Aim 1), we will examine loop dynamics in human induced pluripotent stem cell-derived neurons in response to electrical stimulation, revealing how interaction frequency is functionally connected to transcriptional bursting of immediate early and secondary response genes. On the timescale of hours (Aim 3), we will elucidate how the architectural protein YY1 connects enhancer-promoter loops that re-assemble upon the exit from mitosis by erythroid cells. On the timescale of weeks (Aim 2), we will use a cellular “Time Machine” to longitudinally track the rare cells that undergo cellular reprogramming, allowing us to dissect the functionality of loop formation and dissolution with single-cell and subcellular resolution during the reprogramming of somatic cells to pluripotency and transition of melanoma cancer cells to a resistant phenotype. Our team consists of a highly productive and collaborative set of junior and senior investigators with complementary expertise and overlapping interests, including Dr. Gerd Blobel (epigenetics, mitosis, loop engineering), Dr. Eric Joyce (Oligopaints imaging), Dr. Bomyi Lim (nascent transcript live cell imaging), Dr. Jennifer Phillips-Cremins (chromatin architecture, loop engineering, neurobiology), Dr. Stanley Qi (CRISPR genome engineering, live cell imaging), and Dr. Arjun Raj (single cell genomics, RNA imaging, reprogramming). We will develop and apply live and fixed cell imaging techniques for chromatin contacts, and in the same cells image nascent transcription. We will build a cadre of synthetic architectural proteins to engineer loops in a time-dependent inducible manner. Successful application of our engineering and imaging tools across biological systems will yield a comprehensive and rigorous assessment of the cause-and-effect relationship between loops and distinct biological phenotypes across timescales.
哺乳动物基因组折叠成数以万计的远程环相互作用。一个

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)

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Gerd A Blobel其他文献

Genome folding dynamics during the M-to-G1-phase transition
M 期到 G1 期转变过程中的基因组折叠动力学
Controlling long-range genomic interactions to reprogram the β-globin locus
  • DOI:
    10.1186/1756-8935-6-s1-o39
  • 发表时间:
    2013-03-01
  • 期刊:
  • 影响因子:
    3.500
  • 作者:
    Wulan Deng;Jeremy W Rupon;Hongxin Wang;Andreas Reik;Philip D Gregory;Gerd A Blobel
  • 通讯作者:
    Gerd A Blobel

Gerd A Blobel的其他文献

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{{ truncateString('Gerd A Blobel', 18)}}的其他基金

Engineering and Imaging 3D genome structure-function dynamics across time scales
工程与成像 跨时间尺度的 3D 基因组结构-功能动态
  • 批准号:
    10456233
  • 财政年份:
    2020
  • 资助金额:
    $ 112.83万
  • 项目类别:
Engineering and Imaging 3D genome structure-function dynamics across time scales
工程与成像 跨时间尺度的 3D 基因组结构-功能动态
  • 批准号:
    10656401
  • 财政年份:
    2020
  • 资助金额:
    $ 112.83万
  • 项目类别:
Engineering and visualizing genome folding at high spatiotemporal resolution
以高时空分辨率对基因组折叠进行工程设计和可视化
  • 批准号:
    10001247
  • 财政年份:
    2019
  • 资助金额:
    $ 112.83万
  • 项目类别:
Engineering and visualizing genome folding at high spatiotemporal resolution
以高时空分辨率对基因组折叠进行工程设计和可视化
  • 批准号:
    9003449
  • 财政年份:
    2015
  • 资助金额:
    $ 112.83万
  • 项目类别:
Engineering and visualizing genome folding at high spatiotemporal resolution
以高时空分辨率对基因组折叠进行工程设计和可视化
  • 批准号:
    9762161
  • 财政年份:
    2015
  • 资助金额:
    $ 112.83万
  • 项目类别:
Engineering and visualizing genome folding at high spatiotemporal resolution
以高时空分辨率对基因组折叠进行工程设计和可视化
  • 批准号:
    9144858
  • 财政年份:
    2015
  • 资助金额:
    $ 112.83万
  • 项目类别:
Engineering and visualizing genome folding at high spatiotemporal resolution
以高时空分辨率对基因组折叠进行工程设计和可视化
  • 批准号:
    9323543
  • 财政年份:
    2015
  • 资助金额:
    $ 112.83万
  • 项目类别:
Functions, mechanisms, and therapeutic potential of chromatin looping
染色质环化的功能、机制和治疗潜力
  • 批准号:
    8714048
  • 财政年份:
    2013
  • 资助金额:
    $ 112.83万
  • 项目类别:
Functions, mechanisms, and therapeutic potential of fetal hemoglobin inducers
胎儿血红蛋白诱导剂的功能、机制和治疗潜力
  • 批准号:
    10308676
  • 财政年份:
    2013
  • 资助金额:
    $ 112.83万
  • 项目类别:
Functions, mechanisms, and therapeutic potential of chromatin looping
染色质环化的功能、机制和治疗潜力
  • 批准号:
    8559656
  • 财政年份:
    2013
  • 资助金额:
    $ 112.83万
  • 项目类别:

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