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.

摘要