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Optogenetic Engineering of 3D Chromatin Architecture

3D 染色质结构的光遗传学工程

基本信息

批准号：
10004126
负责人：
Wenbo Li
金额：
$ 23.06万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
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：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10004126
关键词：
3-Dimensional Address Animals Architecture Base Pairing Biological Biological Process Biological Testing Biology CRISPR/Cas technology Cell physiology Cells Chromatin Chromatin Loop Clustered Regularly Interspaced Short Palindromic Repeats Collection DNA biosynthesis Development Dimerization Disease Elements Engineering Enhancers Eukaryota Fingers Frequencies Future Gene Expression Genes Genetic Transcription Genome Goals Human Cell Line In Vitro Individual Intervention Kinetics Knowledge Laboratories Left Length Light Malignant Neoplasms Methods Molecular Biology Molecular Conformation Neisseria meningitidis Nuclear Oranges Outcome Pathologic Phototherapy Play Population Proteins RNA Interference RNA Splicing Regulation Regulatory Element Research Personnel Role Series Streptococcus pyogenes System Technology Transcriptional Regulation Width clinically relevant design developmental disease dimer gain of function gene function genome integrity genomic locus human disease human model in vivo innovation innovative technologies insight interest knock-down loss of function malformation new technology novel nuclease optogenetics overexpression prevent promoter prototype technology development tool

项目摘要

PROJECT SUMMARY / ABSTRACT The organizing principle of chromatin architecture in three dimensions (3D) remains a major mystery in biology. A rapid progress has been made in the last decade to characterize the hierarchies of chromatin architecture, including enhancer-promoter loops, chromatin contact domains, topological domains and chromatin A/B com- partments. Importantly, the alteration of the 3D genome architecture plays an important role in human disease such as developmental disorders and cancer. However, a major current challenge is to determine the biologi- cal importance of each layer of these 3D chromatin architectures, to uncover their causative roles in modulat- ing gene expression and/or other nuclear activities, and to potentially manipulate these architectures for dis- ease intervention. We assembled a strong team of investigators to develop an innovative new toolset to help solve this challenge, which takes advantage of light controllable protein dimers and advanced Crispr/Cas9 ge- nome editing technology. Our goal in this project is to develop the prototype of this toolset that we referred to as PaCIR to create de novo enhancer-promoter loops and topological associated domain that could be rapidly activated and deactivated. The successful execution of this project will provide a highly demanded strategy to study chromatin loops at essentially any specific regions of interests in vitro and in vivo. This toolset is rapid, efficient and non-invasive, which will not only pave way for uncovering profound new insights into chromatin loops and domains in gene transcription control, but also shed lights on a novel concept to rectify disease- associated mal-formation of chromatin architectures.

项目摘要/摘要