Disease Modeling Unit

疾病模型单位

• 批准号: 10670787
• 负责人: Jason D. Heaney
• 金额: $ 52.22万
• 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/10670787
• 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; Genes; Genetic; Glucose; Glucose Intolerance; Goals; Hair; Haplotypes; Heterozygote; Hypodontia; Image; Individual; Infant; Insulin; Intervention; Intervention Studies; Islet Cell; Islets of Langerhans; Kidney; Knock-in; Knock-in Mouse; Knockout Mice; Limb structure; Loss of Heterozygosity; Macaca mulatta; Microphthalmos; Modeling; Modification; Motor; Mus; Neurologic; Neurons; Onset of illness; 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; model organism; mouse model; neurobehavior; neurobehavioral; novel therapeutic intervention; pre-clinical; precision medicine; programs; transcriptome; translational impact; translational potential; treatment optimization; variant of interest; 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精准医学建模中心的疾病建模部门将负责制作 并对中心的精密动物模型进行表型分析。该部门将使用先进的基因组编辑和 我们现有的动物建模程序开发的修饰技术和表型工作流程，以 (1) 产生重现人类疾病相关变异的小鼠和果蝇模型，以及（2）验证变异- 疾病关联，确定疾病机制，并在果蝇和小鼠模型中测试假定的干预措施。 此外，该部门还将筛选恒河猴群体的测序数据，以识别具有假定的动物 感兴趣的基因中与疾病相关的变异。该单位将承担三个示范项目 展示拟建中心对影响多种器官的未确诊和罕见疾病进行建模的能力 不同发病年龄的系统，并将模型生物的发现转化为患者护理。这些 提名项目将把飞行中的机制研究与表型分析和干预研究结合起来 小鼠展示果蝇和小鼠模型的生产能力、表型分析能力的广度，以及 该中心生成的模型的潜在转化影响。与生物信息学一起 临床前/临床联合科室，该部门还将参与人类疾病相关变异提名 通过识别正确的精密动物模型（例如苍蝇、小鼠）和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。该单位还将 评估假定的恒河猴模型是否适用于每个指定的变体。提名时 选择变体进行建模，该股将在项目期间与资源和服务科密切合作 规划以确保选择正确的模型，并制定严格的研究计划。总体而言，目标 使用该单位的精确模型进行的研究将揭示新的疾病机制，揭示新的疾病机制 疾病生物标志物和表型，并为患者确定潜在的新治疗策略。