Disease Modeling Unit

疾病模拟股 高通量测序技术的出现使得人们能够快速发现疾病的遗传原因。 然而，我们将这些发现转化为治疗方法的能力并没有跟上步伐，至少部分原因是， 缺乏精确的、可预测的动物模型，这仍然是转化潜在新技术的关键一步。 用于临床的治疗。小鼠仍然是临床道路上几乎不可或缺的工具 应用程序.遗传学上精确的小鼠模型可以被设计来重现大多数人类疾病 病理学，并因此允许新疗法的详细研究和临床前测试。 JAX在开发和研究人类疾病的小鼠模型方面有着悠久的历史， 致力于建立杰克逊实验室（JAX）精密遗传学中心的承诺、规模和专业知识 （JCPG）。事实上，JAX目前是作为三个精确遗传学试点中心之一（U 54 OD 020351）。JCPG的下一次迭代将建立在这项工作所奠定的基础之上， 在一个赠款周期内，成功地从疾病模型开发到完成 临床前工作现在转向临床试验。现在提出的JCPG基础设施改进、集中和 扩大了对上一个试点项目的成功至关重要的基础设施和服务。下一 JCPG将更好地为我们现有的各种临床合作者提供服务， 生物医学界的大部分。JCPG疾病建模单位（DMU）是启动 一种新的疾病模型。首先与生物信息学核心密切合作， 最佳遗传/基因组设计，然后DMU将通过表型表征指导每个模型 与临床前和临床合作伙伴（JCPG Pre/CoClinical Core）协商， 建立模型，然后将新模型传递给资源和服务核心进行集群维护， 保存和全球发行。 疾病建模单元（DMU）的总体目标是将JCPG核心的操作细化为单个 集成、灵活和有凝聚力的疾病建模管道，可支持 生物医学界。许多关键组件已经到位，因此DMU将专注于构建 计划和项目管理基础设施，以集成创新的新工具和分析平台。 为了实现这一目标，DMU将：1）建立一个全面的精确模型开发和表征 管道，具有规模，管理基础设施和生物信息学工具，以支持外部 从社区提名，2）利用正在进行的JCPG项目，以“播种”管道与“铲准备” 高影响力的项目，将允许管道结构和流程的完善，3）开发和执行 三个示范项目，以扩大JCPG的技术和科学能力，以支持更广泛的 疾病建模的需要。

PROJECT SUMMARY DISEASE MODELING UNIT The advent of high-throughput sequencing has allowed rapid discovery of the genetic causes of disease. However, our ability to translate these discoveries into therapeutics has not kept pace due, at least in part, to a lack of precise, predictive animal models which still serve as a critical step toward translating potential new treatments for use in the clinic. The mouse remains a near indispensable tool on the road to clinical application. Genetically accurate mouse models can be designed to recapitulate most human disease pathology and therefore allow for detailed studies and preclinical testing of novel therapeutics. JAX has a long history of developing and studying mouse models of human disease and the institutional commitment, scale, and expertise to build The Jackson Laboratory (JAX) Center for Precision Genetics (JCPG). Indeed, JAX is currently funded as one of three Pilot Centers for Precision Genetics, (U54 OD020351). The next iteration of the JCPG will build on the groundwork laid by this effort that was able to successfully move, within one grant cycle, from disease model development through completion of the preclinical work to now move toward clinical trials. The JCPG infrastructure now proposed refines, focuses and expands on the infrastructure and services that were essential to the successes of the previous pilot. The next JCPG will serve our existing diverse set of clinical collaborators even better and broaden access for an even larger portion of the biomedical community. The JCPG Disease Modeling Unit (DMU) is key to launching development of a new disease model. Working closely first with the Bioinformatics Core to establish an optimal genetic/genomic design the DMU will then guide each model through phenotypic characterization working in consultation with preclinical and clinical partners (JCPG Pre/CoClinical Core) to validate and establish the model before passing the new model to the Resource and Services Core for colony maintenance, preservation and worldwide distribution. The overall goal of the Disease Modeling Unit (DMU) is to refine the operation of the JCPG Cores into a single integrated, flexible, and cohesive disease modeling pipeline that can support the growing and diverse needs of the biomedical community. Many key components are already in place so the DMU will focus on building the program and project management infrastructure to integrate innovative new tools and analysis platforms. To accomplish this the DMU will: 1) build a comprehensive precision model development and characterization pipeline that has the scale, management infrastructure, and bioinformatics tools to support external nominations from the community, 2) leverage ongoing JCPG projects to “seed” the pipeline with “shovel-ready” high-impact projects that will allow refinement of pipeline structure and processes and, 3) develop and execute three Demonstration Projects to extend JCPG technical and scientific capabilities to support a wider array of disease modeling needs.