Genome Editing Core

基因组编辑核心：摘要 研究糖尿病及其并发症的潜在机制需要相关的实验模型。 基因组编辑核心（GEC）的建立是为了帮助研究人员生成细胞和小鼠模型 这可以加速开发新的预防、治疗和最终治愈方法， 糖尿病GEC为研究人员提供工具和专业知识，以利用最新的CRISPR方法 用于产生小鼠和细胞模型。这个核心的第一个组成部分， 大约5年前，是一个小鼠基因组编辑服务。GEC工作人员协助研究人员设计和 生成具有多种基因插入、缺失和修饰的定制小鼠模型。全球环保法庭 是独一无二的定位工程基因组的最相关的小鼠模型的糖尿病，包括 用于1型糖尿病的非肥胖糖尿病小鼠模型和用于2型糖尿病研究的品系（例如C57BL 6 和C57BLKS）。这些模型使研究人员能够评估基因组编辑的后果， 在生理条件下的系统水平。这个核心的第二个组成部分使强大的基于细胞的， 通过CRISPR筛选服务进行基因组规模的前向遗传筛选， 以满足乔斯林研究基地的需求。GEC领导层在这方面拥有出色的专业知识， 在过去的一年里，核心已经获得了几个基因组规模的小鼠和人类CRISPR 库和完成的成功屏幕。在本申请中，CRISPR筛选服务将在 提供在许多不同的细胞类型中进行全基因组筛选，以揭示机制并识别 糖尿病及其并发症发病机制的新靶点。总而言之，GEC提供了最先进的 DRC研究人员的平台，以小规模操纵小鼠和人类细胞的基因组， 假设驱动的项目和大规模的探索性，假设生成的研究工作。的 GEC还允许研究人员在小鼠模型中测试基因组编辑，以探索系统性基因功能。 在生理条件下。

GENOME EDITING CORE: Abstract Investigating mechanisms that underlie diabetes and its complications requires relevant experimental models. The Genome Editing Core (GEC) was established to assist investigators in generating cell and mouse models that can accelerate the development of new approaches to prevention, treatment, and ultimately a cure for diabetes. The GEC provides investigators the tools and expertise to leverage the latest CRISPR methodologies for the generation of both mouse and cellular models. The first component of this core, implemented approximately 5 years ago, is a mouse genome editing service. GEC staff assist investigators in the design and generation of custom mouse models with gene insertions, deletions and modifications of many kinds. The GEC is uniquely positioned to engineer the genome of the most relevant mouse models for diabetes, including the nonobese diabetic mouse model for type 1 diabetes and strains used in type 2 diabetes research (e.g. C57BL6 and C57BLKS). These models enable investigators to evaluate the consequences of genome edits at the systemic level in physiological conditions. The second component of this core enables powerful cell-based, genome-scale forward genetic screens through a CRISPR screening service and represents a major core evolution to meet the needs of the Joslin research base. GEC leadership brings outstanding expertise in this approach, and over the past year the core has acquired several genome-scale mouse and human CRISPR libraries and completed successful screens. In the present application, CRISPR screening services will be offered to perform genome-wide screens in the many various cell types to uncover mechanisms and identify novel targets in the pathogenesis of diabetes and its complications. In sum, the GEC provides a state-of-the art platform for DRC investigators to manipulate the genome of mouse and human cells at a small scale for specific hypothesis-driven projects and at a large scale for exploratory, hypothesis-generating research endeavors. The GEC further allows investigators to test genome edits in mouse models to explore gene function at the systemic level in physiological conditions.