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Fully Automated Angiogenesis Drug Discovery Assay in Zebrafish

斑马鱼全自动血管生成药物发现测定

基本信息

批准号：
8441500
负责人：
ANTHONY A Ferrante
金额：
$ 50.84万
依托单位：
PHYSICAL SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8441500
关键词：
Affect Algorithms Angiogenesis Promoter Animals Automation Biological Assay Birth Blood Vessels Clinic Clinical Management Collection Common Neoplasm Computer software Data Defect Deformity Development Disease Dose Embryo Embryonic Development Ensure Environment Evaluation FDA approved Fertilization Fishes Fluorescence Microscopy Government Green Fluorescent Proteins Heart Hemangioma Hour Image Imagery Inborn Genetic Diseases Individual Infant Laboratories Larva Lead Letters Libraries Life Location Macular degeneration Malignant Neoplasms Medical Methods Metric Microscope Modeling Mutation Patients Pattern Persons Phase Phenotype Positioning Attribute Preclinical Drug Evaluation Probability Process Research Software Tools Testing Therapeutic Time Vascular Endothelium Wisconsin Zebrafish angiogenesis assay development base computerized data processing drug development drug discovery high throughput screening human disease image processing improved infancy instrumentation interest malformation medical schools mutant new growth novel physical science programs repaired research study small molecule software development tool

项目摘要

DESCRIPTION (provided by applicant): The zebrafish, Danio rerio, has become widely accepted as a model for human disease. Small molecule screens have been performed to identify modifiers of vascular patterning but this process has been performed at relatively low throughput since the tools for fully automated processing are not yet available. We propose to develop a novel, high-throughput screening assay for angiogenesis promoters. The assay would be based on the use of the SideView" microplate to collect clear images of the vascular pattern in animals that express GFP in their vasculature. During Phase I we: 1) developed novel methods to modulate angiogenesis promoters in the plexus; 2) developed software that locates the zebrafish, identifies the region of interest, and moves that region to the center of the field of view; and 3) developed automated, post-acquisition image processing software that distinguishes wild-type zebrafish embryos from xxx mutant embryos with deformities in the plexus. During Phase II the methods, software and instrumentation will be fully integrated and the assay will be validated in a model screen using the Prestwick Library of FDA- approved compounds.

描述（由申请人提供）：斑马鱼Danio rerio已被广泛接受为人类疾病的模型。已经进行了小分子筛选以鉴定血管图案化的修饰剂，但是由于用于全自动处理的工具尚不可用，因此该过程以相对低的通量进行。我们建议开发一种新的，高通量筛选血管生成促进剂的检测方法。该测定将基于使用SideView微孔板来收集在其脉管系统中表达GFP的动物的脉管模式的清晰图像。在第一阶段，我们：1）开发了调节神经丛中血管生成启动子的新方法; 2）开发了定位斑马鱼、识别感兴趣区域并将该区域移动到视野中心的软件;以及3）开发了自动化的采集后图像处理软件，其将野生型斑马鱼胚胎与神经丛中具有畸形的xxx突变胚胎区分开。在第二阶段，方法、软件和仪器将被完全整合，并且将使用FDA批准的化合物的Prestwick库在模型筛选中验证测定。