Disease Modeling Unit

疾病模型单位

• 批准号: 10469586
• 负责人: Stephen A Murray
• 金额: $ 108.39万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469586
• 关键词: Alleles; Animal Model; Bioinformatics; Biological Models; Biometry; CRISPR/Cas technology; Clinic; Clinical; Clinical Research; Clinical Trials; Collection; Communities; Consultations; Development; Disease; Disease model; Faculty; Funding; Genes; Genetic; Genetic Engineering; Genomics; Goals; Grant; High-Throughput Nucleotide Sequencing; Individual; Infrastructure; Intervention; Laboratories; Laboratory mice; Leadership; Maintenance; Modeling; Mus; Mutant Strains Mice; Outcome; Pathology; Phenotype; Physiology; Preclinical Testing; Process; Recording of previous events; Research; Research Personnel; Resource Development; Resources; Seeds; Services; Structure; System; Technology; Testing; The Jackson Laboratory; Therapeutic; Time; Translating; United States National Institutes of Health; Validation; Work; addiction; base; bioinformatics tool; clinical application; cohesion; community engagement; design; flexibility; human disease; human model; improved; innovation; knockout gene; model design; model development; mouse model; neurogenetics; novel therapeutics; operation; pre-clinical; precision genetics; preclinical study; preservation; programs; repository; success; tool

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.

项目摘要疾病建模单元 高通量测序的出现使得快速发现疾病的遗传原因成为可能。 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，至少部分是由于 缺乏精确的、预测性的动物模型，而这些模型仍然是转化潜在新产品的关键一步。 临床上使用的治疗方法仍然是临床道路上不可或缺的工具。 可以设计遗传精确的小鼠模型来重现大多数人类疾病。 病理学，因此可以对新疗法进行详细研究和临床前测试。 JAX在开发和研究人类疾病小鼠模型方面拥有悠久的历史和机构 建立杰克逊实验室 (JAX) 精准遗传学中心的承诺、规模和专业知识 事实上，JAX 目前是三个精准遗传学试点中心之一（U54）。 JCPG 的下一次迭代将建立在这一努力所奠定的基础上，从而能够 在一个资助周期内成功地从疾病模型开发过渡到完成 JCPG 基础设施现在建议对临床前工作进行改进、重点关注和改进。 扩展了对上一个试点的成功至关重要的基础设施和服务。 JCPG 将更好地为我们现有的多元化临床合作者提供服务，并扩大访问范围，以实现更公平的合作 JCPG 疾病模型单元 (DMU) 是启动的关键。 首先与生物信息学核心密切合作，建立一个新的疾病模型。 最佳的遗传/基因组设计，DMU 将指导每个模型进行表型表征 与临床前和临床合作伙伴（JCPG Pre/CoClinical Core）协商以验证和 在将新模型传递到资源和服务核心进行集群维护之前建立模型， 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 集成的、灵活的、有凝聚力的疾病建模管道，可以支持日益增长和多样化的需求 生物医学界的许多关键组成部分已经到位，因此 DMU 将专注于建设 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) 建立全面的精密模型开发和表征 具有规模、管理基础设施和生物信息学工具来支持外部的管道 来自社区的提名，2) 利用正在进行的 JCPG 项目为管道“播种”“准备就绪” 高影响力项目将允许改进管道结构和流程，3）开发和执行 三个示范项目旨在扩展 JCPG 的技术和科学能力，以支持更广泛的领域 疾病建模需求。