HIGH-THROUGHPUT HIGH-CONTENT PLATFORM FOR IMAGE-BASED SCREENS

用于基于图像的屏幕的高通量高内容平台

基本信息

批准号：
8152121
负责人：
Hang Lu
金额：
$ 17.7万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8152121
关键词：
Affect Agar Aging Algorithms Alzheimer&apos s Disease Animal Model Animals Area Arts Automation Behavior Biological Assay Caenorhabditis elegans Candidate Disease Gene Cell Count Cells Cessation of life Chromosomes Custom Data Development Device Designs Diabetes Mellitus Disadvantaged Disease Drosophila melanogaster Drug Industry Engineering Fill-It Fishes Generic Drugs Genes Genetic Genetic Models Genetic Research Genetic Screening Genomics Goals Human Image Imaging Device Individual Intervention Knowledge Libraries Life Link Liquid substance Longevity Manuals Mental disorders Metabolic Metabolic Diseases Methods Metric Microfluidic Microchips Microfluidics Microscopy Molecular Molecular Genetics Nature Nematoda Nerve Degeneration Nervous system structure Neurobiology Optics Organism Output Pathway interactions Pharmacologic Substance Phenotype Positioning Attribute Preclinical Drug Evaluation Process Proteins Public Health RNA Interference Reagent Reproduction Research Robot Sampling Screening procedure Soil Speed Supervision Synapses Synaptic Transmission System Techniques Technology Therapeutic Time Training Vision Visual Work base chemical genetics design direct application fly genome-wide high throughput screening human disease image processing in vivo information gathering innovation interest motor control nervous system disorder neurogenetics novel operation positional cloning public health relevance research study small molecule libraries success synaptic function therapeutic development therapeutic target tool transmission process

项目摘要

DESCRIPTION (provided by applicant): Many human diseases including neurological diseases, diabetes, and diseases associated with aging are molecular and genetic in nature. To fundamentally understand these diseases and to discover pharmaceutical interventions, screening large libraries of reagents using assays in model genetic systems (including worms, flies, and fish) is not only a viable but fruitful approach. The current bottlenecks, however, are in the manual and semi-quantitative techniques such as visual screens or image-based screens, often limiting both the throughput of the experiments; in addition, it is practically impossible or very difficult to use large reagent libraries in conjunction with these assays. Our long- term objective is to develop and use engineering-enabled high-throughput and high-content methods to speed up the discovery processes using model organisms. The objective of this project is to develop a novel high-throughput quantitative method combining microfluidics and automation for studying genes involved in synaptic transmission functions. Genes and pathways emerging from this study could potentially become targets of therapeutics in neurological disorders. The approach is innovative because the technology developed here dramatically increases the capabilities of existing screening tools, and is widely applicable to a variety of problems in different experimental systems. The proposed research is significant because it fills a technology gap in high-throughput and high-content screens, and a knowledge gap in genes and pathways in synaptic transmission. PUBLIC HEALTH RELEVANCE: Synapse transmission is an important and active area of research linking genes to the functions of synapses and the nervous system. It has direct applications to many human diseases such as dysfunctional motor control and mental illnesses.

描述（由申请人提供）：许多人类疾病，包括神经系统疾病、糖尿病和与衰老相关的疾病，本质上都是分子和遗传的。为了从根本上了解这些疾病并发现药物干预措施，使用模型遗传系统（包括蠕虫、苍蝇和鱼类）中的检测方法筛选大型试剂库不仅是一种可行且富有成效的方法。然而，当前的瓶颈在于手动和半定量技术，例如视觉屏幕或基于图像的屏幕，通常限制了实验的吞吐量；此外，将大型试剂库与这些测定结合使用实际上是不可能或非常困难的。我们的长期目标是开发和使用工程支持的高通量和高内涵方法，以加快使用模式生物的发现过程。该项目的目标是开发一种结合微流体和自动化的新型高通量定量方法，用于研究涉及突触传递功能的基因。这项研究中出现的基因和通路可能成为神经系统疾病的治疗目标。该方法具有创新性，因为这里开发的技术极大地提高了现有筛选工具的能力，并且广泛适用于不同实验系统中的各种问题。这项研究意义重大，因为它填补了高通量和高内涵筛选的技术空白，以及突触传递基因和途径的知识空白。公共卫生相关性：突触传递是将基因与突触和神经系统功能联系起来的一个重要且活跃的研究领域。它可直接应用于许多人类疾病，例如运动控制功能障碍和精神疾病。