Disease Modeling Unit

摘要 BCM精确医学建模中心的疾病模型股将负责制作 并对中心的精密动物模型进行表型鉴定。该股将使用先进的基因组编辑和 由我们现有的动物建模程序开发的修改技术和表型工作流程，以(1) 制作小鼠和苍蝇模型，概括人类疾病相关的变种，以及(2)验证变种- 疾病关联，确定疾病机制，并在苍蝇和小鼠模型中测试假定的干预措施。 此外，该股将对恒河猴群体的测序数据进行筛选，以识别可能患有 感兴趣基因中与疾病相关的变异。该股将开展三个预期的示范项目 展示拟建中心对影响各种器官的未诊断和罕见疾病进行建模的能力 在不同的发病年龄使用不同的系统，并将模型生物体的发现转化为病人护理。这些 提名项目将把飞行中的机械学研究与表型和干预研究结合在一起 展示苍蝇和老鼠模型的生产能力，广度的表型能力，以及 中心生成的模型的潜在翻译影响。与生物信息学和 临床前/共同临床科，该股还将参加人类疾病相关变体提名 通过识别正确的精确动物模型(例如，苍蝇、老鼠)和通过识别表型来进行过程 回答本地和外部提名者提出的临床相关问题的策略。该股还将 评估每个被提名的变种是否有一个假定的恒河猴模型可用。被提名时 选择变种进行建模，该股将在项目期间与资源和服务科密切合作 制定计划，确保选择正确的模型，并制定严格的学习计划。总体而言，目标是 使用该单位的精确模型进行的研究将揭示新的疾病机制，揭示新的 疾病生物标志物和表型，并为患者确定潜在的新治疗策略。

ABSTRACT The Disease Modeling Unit of the BCM Center for Precision Medicine Modeling will be responsible for producing and phenotyping the Center’s precision animal models. The Unit will use advanced genome editing and modification techniques and phenotyping workflows developed by our existing animal modeling programs to (1) produce mouse and fly models that recapitulate human disease-associated variants and (2) validate variant- disease associations, identify disease mechanisms, and test putative interventions in fly and mouse models. Moreover, the Unit will screen sequencing data from rhesus macaque colonies to identify animals with putative disease-associated variants in genes of interest. The Unit will undertake three Demonstration Projects intended to showcase the proposed Center’s ability to model undiagnosed and rare diseases affecting a variety of organ systems at different ages of onset and to translate model organism findings back to patient care. These nomination projects will integrate mechanistic studies in the fly with phenotyping and intervention studies in the mouse to demonstrate the fly and mouse model production capacity, breadth of phenotyping capabilities, and potential translational impact of models generated by the Center. Together with the Bioinformatics and Preclinical/Co-Clinical Sections, the Unit will also participate in the human disease-associated variant nomination process by identifying the correct precision animal model (e.g. fly, mouse) and by identifying phenotyping strategies that answer clinically relevant questions posed by local and external nominators. The Unit will also assess whether a putative rhesus macaque model is available for each nominated variant. When nominated variants are selected for modeling, the Unit will work closely with the Resource and Service Section during project planning to ensure that the correct models are selected, and a rigorous study plan is enacted. Overall, the goal of studies performed using the Unit’s precision models will be to uncover new disease mechanisms, reveal new disease biomarkers and phenotypes, and identify potential new therapeutic strategies for patients.