CEGS: Center for Synthetic Regulatory Genomics - Renewal

CEGS：合成监管基因组学中心 - 更新

• 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
• 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

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.

合成调控基因组学中心（Center for Synthetic Regulatory Genomics） 摘要 合成调控基因组学中心（SyRGe）的任务是开发和 应用革命性的技术，使戏剧性的，协调的变化， 以50-1000 kb的大DNA形式存在的广泛基因座，这使得广泛的 调控序列功能的研究和促进翻译的应用 到生物技术，个性化医疗和积极人性化的小鼠模型。 具体而言，我们会（i）加强设计、建造及交付的技术管道， 使其更加高效和精确，ii）实现“自下而上”的完全合成监管 景观，以及细胞和动物的多位点工程，最终在 研究大脑功能和行为的项目iii）在 大DNA水平，iv）开发新的工具来设计哺乳动物的巨大变化 以基因座不可知的方式研究基因组，以及v）开发成像技术， 我们正在运送的大DNA分子。 该中心将大大取代目前和预测的技术， 操纵和评估大DNA。其中一些工作将最终在 生产广泛的人源化动物模型，称为基因组重写， 定制的基因工程小鼠模型（GREAT-GEMM），我们的一个元素 值得进行生物伦理学辩论和讨论的项目。该中心还设有一个独特的 一个非常成功的外展计划， 背景在基因组组装中起着至关重要的作用， 让来自其他领域的研究人员和学生接触变革性的新技术， 促进其颁布整个更大的人类遗传学，模式生物， 基因组学社区最后，确保长期可持续获得 该中心开发的技术已向任何希望部署该技术的人提供， 落实到位。