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：合成调节基因组学中心抽象的合成调节基因组学中心（Syrge）的任务是发展和革命性技术的应用来进行戏剧性的，协调的更改大型基因座的大型DNA的形式为50-1000 kb，这使得广泛调查调节序列和促进翻译应用的功能用于生物技术，个性化医学和积极的人性化小鼠模型。具体来说，我们将（i）增强我们的设计 - 构建 - 交付技术管道使其更加有效，更精确，ii）启用“自下而上”完全合成调节景观以及细胞和动物的多焦点工程，最终导致研究大脑功能和行为的项目iii）在大型DNA的水平，iv）开发新工具来设计哺乳动物的巨型Babase更改基因组以基因义的方式和v）开发成像技术来“点亮” 我们正在传递的大DNA分子。该中心将极大地呈现并预测大型DNA的操纵和评估。其中一些工作将在生产称为基因组改造的广泛人文化的动物模型和量身定制的基因工程鼠标模型（Greatmms），这是我们的元素值得生物伦理辩论和讨论的计划。该中心还具有独特的以及非常成功的外展计划，该计划的本科生来自潜水员背景在基因组议会中起着至关重要的作用，以及研究员计划将研究人员和学生从其他领域暴露于变革性的新技术，促进其在更大的人类遗传学，模型生物和基因组学群落。最后，确保长期可持续访问的机制该中心在该中心开发的技术向任何希望部署它的人已经放置。