Disease Modeling Unit

疾病模型单位

• 批准号: 10259809
• 负责人: Jason D. Heaney
• 金额: $ 49.18万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10259809
• 关键词: 17q12; AXIN2 gene; Adult; Affect; Age of Onset; Alleles; Animal Model; Animals; Ataxia; Atrophic; Back; Bioinformatics; Biological Markers; Brain imaging; Calcium Channel; Calcium Channel Blockers; Choanal Atresia; Clinical; Coloboma; Colorectal Cancer; Complex; Data; Data Collection; Defect; Development; Diabetes Mellitus; Disease; Disease model; Dominant-Negative Mutation; Dysplasia; Early Intervention; Embryo; Ensure; Genes; Genetic; Glucose; Glucose Intolerance; Goals; Hair; Haplotypes; Hypodontia; Image; Individual; Infant; Insulin; Intervention; Intervention Studies; Islet Cell; Islets of Langerhans; Kidney; Knock-in; Knock-in Mouse; Knockout Mice; Limb structure; Macaca mulatta; Microphthalmos; Modeling; Modification; Motor; Mus; Neurologic; Neurons; Onset of illness; Ophthalmology; Patient Care; Patients; Pharmaceutical Preparations; Phenotype; Play; Process; Production; Rare Diseases; Recurrence; Resources; Risk; Role; SHFM1 gene; Services; Severities; Signal Transduction; Syndrome; Techniques; Testing; Therapeutic; Translating; Variant; WNT Signaling Pathway; Work; beta catenin; body system; clinically relevant; craniofacial; data access; data submission; diabetes risk; early onset; fly; gain of function; genome editing; human disease; informatics infrastructure; interest; loss of function; maturity onset diabetes of the young; mouse model; neurobehavior; neurobehavioral; novel therapeutic intervention; pre-clinical; precision medicine; programs; transcriptome; translational impact; treatment optimization; voltage

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.

抽象的 BCM精密医学模型中心的疾病建模单元将负责生产 并表现出中心的精密动物模型。该单元将使用高级基因组编辑和 我们现有的动物建模计划开发的修改技术和表型工作流程（1） 产生的小鼠和蝇模型概括了与人类疾病相关的变体，（2）验证变异 疾病关联，鉴定疾病机制并在蝇模和小鼠模型中测试推定的干预措施。 此外，该单元将筛选从恒河猕猴菌落中的测序数据，以识别具有推定的动物 感兴趣基因的疾病相关变体。该部门将进行三个示威项目 展示拟议中心对影响各种器官的未诊断和罕见疾病建模的能力 不同年龄的系统，并将模型生物体发现转换回患者护理。这些 提名项目将将机械研究与表型和干预研究合并于 鼠标证明苍蝇和鼠标模型的生产能力，表型能力的广度以及 中心产生的模型的潜在翻译影响。以及生物信息学和 临床前/共同链接部分，该单元还将参与与人类疾病相关的变体提名 通过识别正确的精密动物模型（例如飞行，鼠标）和识别表型来进行过程 回答本地和外部提名人所假定的临床相关问题的策略。该单位也将 评估是否适用于每个提名变体的推定恒河猕猴模型。提名 选择了用于建模的变体，该单元将与项目期间的资源和服务部分紧密合作 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 使用该单元的精确模型进行的研究将是揭示新的疾病机制。 疾病生物标志物和表型，并确定患者的潜在新疗法策略。