Tools For Imaging the Functional Genome in Living Cells and Tissues

活细胞和组织中功能基因组成像的工具

基本信息

批准号：
9302783
负责人：
Xavier Darzacq
金额：
$ 85万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9302783
关键词：
4D Imaging Actins Affect Animals Architecture Binding Binding Sites Biophotonics Biosensor Brain California Cell Line Cell Nucleus Cell division Cells Collaborations Color Communities Computer software DNA Development Dimensions Disease Enhancers Event Fluorescent Dyes Foundations Frequencies Functional Imaging Funding Generations Genes Genetic Transcription Genome Genome Mappings Goals Histones Image Imaging Device Individual Label Letters Light Lip structure Location Long-Term Effects Maps Medicine Messenger RNA Microscope Microscopic Microscopy Modification Monoclonal Antibodies Normal Cell Nuclear Optics Organism Participant Phage Display Phototoxicity Process Property Protocols documentation Reagent Recording of previous events Regulation Reporting Research Research Personnel Resolution Resource Sharing Resources Role SP1 gene Site Speed Technology Testing Time Tissues Transcriptional Activation Transcriptional Regulation Transgenic Animals Transgenic Organisms Universities Validation Work Zebrafish adaptive optics animal imaging animal tissue college design embryonic stem cell epigenetic regulation experimental study histone modification imaging platform instrument interest molecular imaging novel particle promoter public health relevance single molecule stem cell differentiation tool transcription factor two-photon whole genome

项目摘要

DESCRIPTION (provided by applicant): This goal of this proposal is to develop imaging tools capable of imaging the functional genome by mapping the three dimensional binding sites and clustering of transcription factors and histone modifiers. We will use single molecule particle tracking within the entire nucleus of the cell in real time. Initially this will be done in culture ES cells, and ultimately in living animals. There will be three locations involved: Albert Einstein College of Medicine, the University of California at Berkeley and the Janelia Research Campus of the HHMI, where the Transcription Imaging Consortium integrates the efforts of the investigators of this proposal. The reagents will be developed at Einstein and Berkeley and the microscope technology that has been developed and used predominantly at Janelia, will inform further modifications in building similar microscopes at Berkeley and Einstein. Genes of interest will be marked to image promoter-enhancer interactions in cells, tissues and organisms with high resolution. The microscopes employed and developed for these applications will be the multifocal microscope, the lattice light sheet microscope, the adaptive optics microscope and the high-speed three-color super registration microscope. Importantly, we will evaluate the levels of phototoxicity for the imaging protocols on each microscope and develop approaches to minimize it. Microscopes developed will be made available to the Nucleome community at the Einstein and Berkeley sites and at Janelia through a resource sharing facility, the Advanced Imaging Center, supported by the HHMI and the Moore Foundation with the explicit purpose of disseminating the use of the technology. No funds are requested for the Janelia component of this proposal. All funds will be for development of microscopes and reagents that will be at Berkeley and Einstein.

描述（由适用提供）：该提案的这个目标是开发能够通过映射三维结合位点以及转录因子和组蛋白修饰剂的聚类来成像功能基因组的成像工具。我们将实时使用单个分子粒子跟踪。最初，这将在培养ES细胞中，最终在活动物中完成。将涉及三个地点：阿尔伯特·爱因斯坦医学院，加利福尼亚大学伯克利分校和HHMI的Janelia Research Campus，转录成像联盟在此融合了该提议研究人员的努力。这些试剂将在爱因斯坦和伯克利以及主要在Janelia开发和使用的显微镜技术开发，将为在伯克利和爱因斯坦建造类似显微镜的进一步修改提供信息。感兴趣的基因将标记为具有高分辨率的细胞，组织和组织中的图像启动子增强剂的相互作用。用于这些应用并开发的显微镜将是多灶显微镜，晶格光片显微镜，自适应光学显微镜和高速三色超级登记显微镜。重要的是，我们将评估每个显微镜上成像方案的光毒性水平，并开发最小化的方法。开发的显微镜将提供给爱因斯坦和伯克利站点的核心社区，并通过资源共享设施，由HHMI和Moore基金会支持的高级成像中心，并明确目的是散布技术的使用。该提案的Janelia组成部分不要求资金。所有资金将用于开发伯克利和爱因斯坦的显微镜和试剂。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recent evidence that TADs and chromatin loops are dynamic structures.

DOI：
10.1080/19491034.2017.1389365
发表时间：
2018-01-01
期刊：
Nucleus (Austin, Tex.)
影响因子：
0
作者：
Hansen AS;Cattoglio C;Darzacq X;Tjian R
通讯作者：
Tjian R

Nuclear microenvironments modulate transcription from low-affinity enhancers.

核微环境调节低亲和力增强子的转录。

DOI：
10.7554/elife.28975
发表时间：
2017
期刊：
eLife
影响因子：
7.7
作者：
Tsai,Albert;Muthusamy,AnandK;Alves,MarianaRp;Lavis,LukeD;Singer,RobertH;Stern,DavidL;Crocker,Justin
通讯作者：
Crocker,Justin

Transvection Goes Live-Visualizing Enhancer-Promoter Communication between Chromosomes.

横传实时可视化染色体之间的增强子-启动子通讯。

DOI：
10.1016/j.molcel.2018.04.004
发表时间：
2018
期刊：
Molecular cell
影响因子：
16
作者：
Tsai,Albert;Singer,RobertH;Crocker,Justin
通讯作者：
Crocker,Justin

Imaging dynamic and selective low-complexity domain interactions that control gene transcription.

DOI：
10.1126/science.aar2555
发表时间：
2018-07-27
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
Chong S;Dugast-Darzacq C;Liu Z;Dong P;Dailey GM;Cattoglio C;Heckert A;Banala S;Lavis L;Darzacq X;Tjian R
通讯作者：
Tjian R

Imaging Transcription: Past, Present, and Future.