Disease Modeling Unit

项目总结疾病建模单元 高通量测序的出现使人们能够迅速发现疾病的遗传原因。 然而，我们将这些发现转化为治疗学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，这些模型仍然是转换潜在新技术的关键步骤 临床上使用的治疗方法。在通往临床的道路上，鼠标仍然是几乎不可或缺的工具 申请。基因上准确的小鼠模型可以被设计成概括大多数人类疾病 因此，可以对新的治疗方法进行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和机构 致力于建立杰克逊实验室(JAX)精确遗传学中心的承诺、规模和专业知识 (JCPG)。事实上，日本宇宙航空研究开发机构目前是作为三个精密遗传学试点中心之一获得资助的(U54 OD020351)。联合联络小组的下一次迭代将建立在这一努力奠定的基础上，这一努力能够 在一个赠款周期内，成功地从疾病模型开发到完成 临床前工作现在正在进行临床试验。中英联合联络小组现在提议的基础设施完善、集中和 扩展了对前一次试点的成功至关重要的基础设施和服务。下一个 JCPG将为我们现有的不同的临床合作者提供更好的服务，并为我们提供更广泛的机会 更大比例的生物医学界。JCPG疾病建模单位(DMU)是推出 开发一种新的疾病模型。首先与生物信息学核心密切合作，建立 最优的遗传/基因组设计然后DMU将通过表型特征来指导每个模型 与临床前和临床合作伙伴(JCPG Pre/CoClinic Core)协商，以验证和 在将新模型传递给资源和服务核心进行集群维护之前建立模型， 保存并在全球范围内分发。 疾病模型股(DMU)的总体目标是将JCPG核心的操作改进为单一的 集成、灵活且有凝聚力的疾病建模渠道，可支持不断增长的多样化需求 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。 为了实现这一点，DMU将：1)建立一个全面的精密模型开发和表征 拥有规模、管理基础设施和生物信息学工具以支持外部 来自社区的提名，2)利用正在进行的中日合作伙伴关系项目，为管道“播种”“准备就绪” 将允许改进管道结构和流程的高影响项目，以及3)开发和执行 三个示范项目，以扩展中日合作伙伴关系的技术和科学能力，以支持更广泛的 疾病建模需要。

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.