quantitative microscopy-based rapid phenotyping and screening

基于定量显微镜的快速表型分析和筛选

• 批准号: 8108756
• 负责人: Hang Lu
• 金额: $ 27.42万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8108756
• 关键词: Age; Aging; Algorithms; Animals; Apoptosis; Area; Automation; Biological Models; Caenorhabditis elegans; Classification; Collection; Computer Assisted; Computers; Data; Development; Developmental Cell Biology; Device Designs; Devices; Disease; Drosophila genus; Embryo; Engineering; Enhancers; Ensure; Environment; Event; Eye; Fill-It; Fluorescence; Genes; Genetic; Genetic Models; Genetic Research; Genetic Screening; Goals; Image; Image Analysis; Imaging Techniques; Imaging technology; Larva; Lead; Length; Life; Link; Maintenance; Manuals; Measures; Mental disorders; Methods; Metric; Microfluidic Microchips; Microfluidics; Microscopy; Modeling; Molecular; Molecular Biology; Motor Neurons; Mutagenesis; Nematoda; Nerve Degeneration; Nervous system structure; Neurobiology; Neurodegenerative Disorders; Neurons; Neurosciences; Nobel Prize; Optics; Organism; Pathway interactions; Pattern; Phenotype; Phylogeny; Positioning Attribute; Process; Quantitative Microscopy; RNA Interference; Regulatory Pathway; Research; Screening procedure; Shapes; Sorting - Cell Movement; Speed; Standardization; Structure; Synapses; Syncope; System; Techniques; Technology; Testing; Therapeutic; Time; Training; Visual; Work; Zebrafish; age related; base; computerized; design; fly; genome sequencing; human disease; image processing; improved; in vivo; innovation; interest; mutant; nerve injury; nervous system disorder; neurogenetics; new technology; novel; programs; research study; synaptogenesis; therapeutic target; tool; trait

DESCRIPTION (provided by applicant): Synapses are most fundamental to the function of a nervous system. C. elegans is an excellent genetic model system for finding genes and elucidating pathways because of its sequenced genome and the abundance of molecular biology tools and mutants. Due to the simplicity of its nervous system, many breakthroughs have been made in C. elegans for understanding molecular mechanisms in the patterning of the nervous system and synapse development. The current bottlenecks, however, are in the manual and non-quantitative techniques such as visual screens, often limiting both the throughput of the experiments and the phenotypes one can examine. Our long-term objective is to develop technologies to understand how genes, age, and the environment together define and continue to remodel the nervous system of an organism. Microtechnologies are ideal for studies of C. elegans neuroscience because of the relevant length scales and the possibility for automation; similarly quantitative imaging techniques are key to deciphering molecular mechanisms. The objective of this R01 project is to engineer micro devices for large-scale live imaging and quantitative imaging technologies in order to study synapse development in an in vivo system. Genes and pathways emerging from this study could potentially become targets of therapeutics in neurological disorders. We hypothesize that quantitative microscopy-based approaches can indeed enable identification of novel genes and pathways that conventional approaches cannot. The first component of this project is to develop on-chip rapid and high-content in vivo imaging techniques, and in parallel to develop algorithms and quantitative measures for the analysis of such high-content data. The second component of the project is to perform screens and studies using these novel technologies. The approach is innovative because the technology developed here dramatically increases the capabilities of existing imaging and screening tools by several orders of magnitude in speed and much more sensitive and accurate than conventional manual approaches. The proposed research is significant because it fills the urgent need in high-throughput and high-content screens as well as identifying novel genes and pathways. In addition, besides the contribution to the specific neurobiology, the technologies are widely applicable to areas such as developmental cell biology, and to other small organisms such as fly larvae and zebrafish embryos. PUBLIC HEALTH RELEVANCE: Synapse development is an important and active area of research linking genes and environments to the formation and maintenance of synapses in the nervous system. It has direct implications in many human diseases such as neurodegeneration and mental illnesses.

描述（由申请人提供）：突触对于神经系统的功能来说是最基本的。 秀丽隐杆线虫因其基因组测序以及丰富的分子生物学工具和突变体而成为寻找基因和阐明途径的优秀遗传模型系统。 由于其神经系统的简单性，秀丽隐杆线虫在理解神经系统模式和突触发育的分子机制方面取得了许多突破。 然而，当前的瓶颈在于手动和非定量技术，例如视觉筛选，通常限制了实验的吞吐量和可以检查的表型。 我们的长期目标是开发技术来了解基因、年龄和环境如何共同定义并继续重塑生物体的神经系统。 由于相关的长度尺度和自动化的可能性，微技术是线虫神经科学研究的理想选择；类似的定量成像技术是破译分子机制的关键。 该 R01 项目的目标是设计用于大规模实时成像和定量成像技术的微型设备，以研究体内系统中的突触发育。 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。 我们假设基于定量显微镜的方法确实可以识别传统方法无法识别的新基因和途径。 该项目的第一个组成部分是开发片上快速高内涵体内成像技术，同时开发用于分析此类高内涵数据的算法和定量措施。 该项目的第二个组成部分是使用这些新技术进行筛选和研究。 该方法具有创新性，因为这里开发的技术将现有成像和筛查工具的功能大大提高了几个数量级，速度比传统的手动方法更加灵敏和准确。 拟议的研究意义重大，因为它满足了高通量和高内涵筛选以及识别新基因和途径的迫切需求。 此外，除了对特定神经生物学的贡献外，这些技术还广泛适用于发育细胞生物学等领域，以及蝇幼虫和斑马鱼胚胎等其他小型生物体。 公共健康相关性：突触发育是将基因和环境与神经系统中突触的形成和维持联系起来的一个重要且活跃的研究领域。 它对神经退行性疾病和精神疾病等许多人类疾病有直接影响。