CEGS: Center for Synthetic Regulatory Genomics - Renewal

CEGS：合成监管基因组学中心 - 更新

基本信息

批准号：
10652025
负责人：
Jef D BOEKE
金额：
$ 250万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-12 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10652025
关键词：
Affect Animal Model Animals Base Pairing Behavior Binding Biochemical Bioethics Biotechnology Brain Cell Lineage Cells Chromatin Chromosomes Clustered Regularly Interspaced Short Palindromic Repeats Code Collection Communities Complex Coupling Cultured Cells Development Disease Disease model Elements Embryonic Development Engineering Enhancers Ensure Exposure to Failure Fostering Gene Expression Profile Gene Library Genes Genetically Engineered Mouse Genome Genome engineering Genomics Genus Vanilla Haplotypes Human Human Genetics Human Genome Image Imaging technology Investigation Length Libraries Light Mammalian Cell Maps Methodology Minority Modeling Modification Molecular Conformation Mus Nuclear Phase Phenotype Play Positioning Attribute Production Reagent Regulator Genes Regulatory Element Research Research Personnel Resolution Resources Role Services Spottings Students System Technology Untranslated RNA Validation Variant Visualization Work Writing Yeasts Zinc Fingers combinatorial dark matter design functional genomics genome wide association study genomic locus genomic predictors human disease human model humanized mouse improved innovation machine learning prediction mammalian genome member model organism mouse model new technology outreach outreach program personalized medicine portability programs promoter stem cells tool trait translational applications undergraduate student variant of interest vector

项目摘要

Title: Center for Synthetic Regulatory Genomics Abstract The Center for Synthetic Regulatory Genomics (SyRGe) is tasked with development and application of revolutionary technology for making dramatic, coordinated changes to extensive gene loci in the form of Big DNAs of 50-1000 kb, which enable broad investigation of the function of regulatory sequences and foster translational applications to biotechnology, personalized medicine and aggressively humanized mouse models. Specifically, we will (i) enhance our Design – Build – Deliver Technology pipeline ot make it ever more efficient and precise, ii) enable “Bottom up” fully synthetic regulatory landscapes, as well as multilocus engineering in both cells and animals, culminating in projects to look at brain function and behavior iii) deploy combinatorial genomics at the level of Big DNA, iv) Develop new tools to engineer megabase changes to mammalian genomes in a locus-agnostic manner and v) Develop imaging technology to “light up” the Big DNA molecules we are delivering. The Center will dramatically supersede present and predicted technologies for manipulation and assessment of Big DNAs. Some of this work will culminate in the production of extensively humanized animal models called Genomically Rewritten and Tailored Genetically Engineered Mouse Models (GREAT-GEMMs), an element of our program worthy of bioethical debate and discussion. The Center also features a unique and highly successful outreach program whereby undergraduates from diverse backgrounds play a crucial role in genome assembly, as well as a Fellows program to expose researchers and students from other fields to transformative new technology and facilitate its promulgation throughout the larger human genetics, model organism and genomics communities. Finally, mechanisms to ensure long-term sustainable access to the technology developed in this Center to anyone who wishes to deploy it have been put in place.

标题：合成监管基因组学中心抽象的合成监管基因组学中心 (SyRGe) 的任务是开发和应用革命性的技术来做出巨大的、协调的改变 50-1000 kb 大 DNA 形式的广泛基因位点，可实现广泛的基因位点研究调控序列的功能并促进转化应用生物技术、个性化医疗和积极人性化的小鼠模型。具体来说，我们将 (i) 加强我们的设计 - 建造 - 交付技术管道使其更加高效和精确，ii) 实现“自下而上”的完全综合监管景观，以及细胞和动物的多位点工程，最终研究大脑功能和行为的项目 iii) 在大 DNA 水平，iv) 开发新工具来设计哺乳动物的巨碱基变化 v) 开发成像技术来“点亮”基因组我们正在提供大 DNA 分子。该中心将极大地取代现有和预测的技术其中一些工作将在大 DNA 的操纵和评估中达到顶峰。生产基本上人性化的动物模型，称为“基因组重写”和定制的基因工程小鼠模型（GREAT-GEMM）是我们的一个组成部分该中心还有一个独特的特色，值得生物伦理学辩论和讨论。和非常成功的外展计划，因此来自不同领域的本科生背景在基因组组装以及研究员计划中发挥着至关重要的作用让其他领域的研究人员和学生接触变革性的新技术促进其在更大的人类遗传学、模式生物和最后，确保长期可持续获取基因组学社区的机制。该中心开发的技术已向任何希望部署该技术的人提供到位。