Center for Synthetic Regulatory Genomics

修改后的项目摘要/摘要部分 合成调控基因组学中心(SyRGe)的任务是开发和应用革命性技术，对广泛的基因座位进行戏剧性的、协调的改变，这将使对调控序列功能的广泛研究成为可能，并促进生物技术、个性化医学和基因治疗的翻译应用。具体地说，我们将(I)设计和合成超过1000个100kbp的结构，探测精心挑选的一组基因的调控功能；(Ii)开发一条管道，用于在基因组范围内的任何所需位置进行单拷贝整合；(Iii)调查文库对基因表达、染色质特征和核结构的影响；以及(Iv)开发全球计算模型来预测序列变化对基因表达的调控效应。该中心将极大地取代目前和预测的操作和评估调控基因组功能的技术。该中心还包括一个独特且非常成功的外展计划，让来自不同背景的本科生在基因组组装中发挥关键作用，以及一个新的研究员计划，让来自其他领域的研究人员和学生接触到变革性的新技术，并促进其在更大的人类遗传学和基因组学社区中的传播。

Modified Project Summary/Abstract Section 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, which will enable broad investigation of the function of regulatory sequences and foster translational applications to biotechnology, personalized medicine and gene therapy. Specifically, we will (i) design and synthesize over 1000 >100kbp constructs probing regulatory function at a carefully selected set of genes; (ii) develop a pipeline for their single-copy integration at any desired site genome-wide; (iii) survey libraries for effects on gene expression, chromatin features, and nuclear architecture; and (iv) develop global computational models to predict regulatory effects of sequence variation on gene expression. The Center will dramatically supersede present and predicted technologies for manipulation and assessment of regulatory genome function. This Center also incorporates a unique and highly successful outreach program whereby undergraduates from diverse backgrounds play a crucial role in genome assembly, as well as a new Fellows program to expose researchers and students from other fields to transformative new technology and facilitate its promulgation throughout the larger human genetics and genomics communities.