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UAB Childhood Cystic Kidney Disease Core Center (UAB-CCKDCC) - In Vitro Bioassay and Model Development Resource

UAB 儿童囊性肾病核心中心 (UAB-CCKDCC) - 体外生物测定和模型开发资源

基本信息

批准号：
10685989
负责人：
John M Parant
金额：
$ 16.39万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-20 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10685989
关键词：
Adolescent Adult Affect Alleles Bardet-Biedl Syndrome Biological Assay Biosensor CRISPR/Cas technology Categories Cell Line Cells Childhood Cilia Communities Consultations Cyclic AMP Cyst Cystic Kidney Diseases Cystic kidney Data Defect Disease Disease model Drug Screening Engineering Epithelium Fee-for-Service Plans Fingerprint Functional disorder Generations Genes Genetic Genetic Engineering Genetic Fingerprintings Genetic Predisposition to Disease Genome Stability Goals Human In Vitro Individual Joubert syndrome Karyotype Kidney Kidney Diseases Knock-out Laboratories Learning Maintenance Measures Meckel-Gruber syndrome Modeling Molecular Mus Mutation Nephronophthisis Organoids Outcome Pathogenesis Pathway interactions Patients Phase Proteins Quality Control Rattus Reagent Reporter Reproducibility Research Resource Development Resources Signal Pathway Site System Testing Therapeutic Urine Validation Visualization conditional knockout dominant genetic mutation embryonic stem cell experimental study fighting genetically modified cells genome editing improved in vitro Bioassay in vitro Model in vivo in vivo Model induced pluripotent stem cell innovation member model development personalized medicine precision drugs prevent protein transport reagent standardization repaired restoration screening stable cell line tool vector

项目摘要

ABSTRACT (CORE B) Childhood Cystic Kidney Diseases (CCKDs) are debilitating disorders for which there are limited treatments available. The Holy Grail to curing CCKD is to define signaling pathways essential for cyst initiation and subsequent maintenance that can be successfully targeted with therapeutics. In vitro models of CCKD provide a rapid research tool to analyze changes in pathways, to facilitate cellular and protein visualization, are ideal starting points for discovery or validation of hypotheses and are essential for initial testing of potential treatments. Recent advancements in organoid cultures provide an attractive pre-vivo transitional approach to understand CCKD and for second phase testing of potential treatments. Despite the importance of in vitro models for CCKD research there are critical barriers preventing their efficient and effective use: 1) readily available and sharable cell based CCKD resources; 2) careful standardization of reagents that provide rigor and reproducibility across laboratories; and 3) a resource center that facilitates generation of innovative and essential cell based resources for the CCKD research community, without burdening individual labs with the cumbersome learning curve of genome editing, biosensor generation, and quality control assessment. Core B will address these barriers in the following aims: Aim 1 - To Establish In Vitro Biosensors to Study Signaling Pathways Involved in Childhood Cystic Kidney Disorders; Aim 2 – To Genetically Engineer In Vitro Models for CCKD Research; and Aim 3- To Establish and Distribute Critical In Vitro Resources for CCKD Research. Core B acts as an essential bridge between the patient derived studies in the consortium (such as UAB Core A), and the in vivo models generated by the consortium (such as UAB Core C), and therapeutic screening (such as in UAB Core D). Having a centralized CCKD in vitro biosensor and modeling resource will facilitate and enhance research in the greater PKD community and is an essential component of fighting this debilitating disease.

摘要（核心B）儿童囊性肾病（CCKDs）是一种使人衰弱的疾病，治疗方法有限 available.治愈CCKD的圣杯是定义囊肿起始所必需的信号通路，随后的维持，可以成功地用治疗剂靶向。CCKD的体外模型提供了一个快速的研究工具，分析变化的途径，以促进细胞和蛋白质的可视化，是理想的，发现或验证假设的起点，并且对于潜在治疗的初始测试至关重要。类器官培养的最新进展提供了一种有吸引力的体内前过渡方法来理解 CCKD和潜在治疗的第二阶段测试。尽管CCKD体外模型的重要性研究方面存在着严重的障碍，阻碍了它们的高效和有效的用途：1）容易获得和共享基于细胞的CCKD资源; 2）仔细标准化试剂，提供跨实验室;以及3）资源中心，其促进基于细胞的创新和必需资源的产生对于CCKD研究社区来说，无需为单个实验室带来繁琐的学习曲线，基因组编辑、生物传感器生成和质量控制评估。核心B将在以下目的：目的1 -建立体外生物传感器以研究儿童期涉及的信号通路囊性肾疾病;目标2 -CCKD研究的体外基因工程模型;目标3- 建立和分发CCKD研究的关键体外资源。核心B充当重要的桥梁联盟中的患者衍生研究（如UAB Core A）与生成的体内模型之间的差异联合体（如UAB核心C）和治疗筛选（如UAB核心D）。具有集中的CCKD体外生物传感器和建模资源将促进和加强更大范围的研究。 PKD社区，是对抗这种衰弱疾病的重要组成部分。