Quantitative microscopy-based rapid phenotyping and screening

基于定量显微镜的快速表型分析和筛选

基本信息

批准号：
8964929
负责人：
Hang Lu
金额：
$ 30.71万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8964929
关键词：
Address Affect Age Aging Algorithms Alleles Animals Area Automation Biological Models Biology Caenorhabditis elegans Chromosome Mapping Complex Computer Vision Systems Computer software Data Development Developmental Cell Biology Devices Disease Drosophila genus Embryo Engineering Environment Event Eye Fill-It Fluorescence Funding Genes Genetic Genetic Models Genetic Research Genetic Screening Genomic approach Genomics Goals Human Image Imaging Device Imaging Techniques Imaging technology Inbreeding Larva Lead Life Link Maintenance Manuals Maps Measures Mental disorders Methods Microfluidics Microscopy Molecular Molecular Biology Morphology Nematoda Nervous system structure Neurobiology Neurodegenerative Disorders Neurons Organism Pathway interactions Pattern Phase Phenotype Phylogeny Positioning Attribute Quantitative Microscopy Quantitative Trait Loci Regulatory Pathway Research Resolution Schizophrenia Shapes Speed Synapses System Techniques Technology Therapeutic Time Vision Visual Work Zebrafish autism spectrum disorder base design experience fly forward genetics genetic approach genome sequencing high throughput screening human disease improved in vivo in vivo imaging innovation mutant nerve injury nervous system disorder novel programs public health relevance quantitative imaging research study screening success synaptogenesis technology development therapeutic target tool trait

项目摘要

DESCRIPTION: 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 are in the manual and non-quantitative techniques such as visual screens, limiting both the throughput of the experiments and the phenotypes one can examine. Our long-term objective is to develop technologies and to understand how genes, age, and the environment together define and continue to remodel the nervous system of an organism. In the last funding period, we have made large progress in hardware system design (including microtechnologies and automation technologies) and software for quantitative characterization of phenotypes. The objective of this continuation project is to further engineer superior micro devices for large-scale live imaging and quantitative imaging technologies, and combine with the power of genetic and genomic approaches to study synapse development in this in vivo system; genes and pathways emerging from this study could potentially become targets of therapeutics in neurological disorders. We have shown in the previous phase of the project that quantitative microscopy-based approaches can indeed enable identification of novel genes and pathways that conventional approaches cannot. In the continuation phase, we will further optimize on-chip rapid and high-content in vivo imaging techniques, and in parallel further develop algorithms and quantitative measures for the analysis of such high-content data; we will screen based on novel synthetic phenotype unobservable by eye; we will also exploit powerful genomic techniques to identify loci and potential multigenic interactions that shape the synapse morphology. These experimental approaches will identify genes that cannot have been identified otherwise because of the difficulties associated with the phenotypical profiling, but addressed using our engineered techniques here. The approach is innovative because the technology developed here dramatically increases the throughput, sensitivity, and accuracy of the experiments, and truly enables the utility of extremely powerful genetic and genomic methods. 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.

描述：突触是神经系统的功能。突触浮游在手动的非量化技术中，例如视觉筛选，限制了经验的贯穿遍历和人们可以检查的表型。在最后的资金期间在这种体内系统中；这样的高含量数据；我们将不可观察的表型；表型的特征，但在这里使用我们的ECTEARIQUE，在这里开发了跨度和实验的准确性，而Trury可以实现F极有效的遗传和基因组方法。筛选的小说和途径。