Development of on-chip ultra high-throughput whole-animal assay technologies

片上超高通量全动物检测技术的开发

基本信息

批准号：
7431027
负责人：
Mehmet Fatih Yanik
金额：
$ 251.75万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7431027
关键词：
Ablation Accounting Address Adult Adverse effects Affect Afferent Neurons Age Aging Algorithms Alzheimer&apos s Disease American Amyotrophic Lateral Sclerosis Anesthetics Animal Model Animals Area Arts Automated Pattern Recognition Automobile Driving Award Axon Axotomy Back Behavior Behavioral Behavioral Assay Biochemical Biochemical Genetics Bioinformatics Biological Biological Assay Biological Models Biological Neural Networks Biological Sciences Biology Biophotonics Blood flow Brain C. elegans genome Caenorhabditis elegans Candidate Disease Gene Cell Death Cell Line Cell membrane Cells Central Nervous System Diseases Centrifugation Cessation of life Chemical Injury Chemicals Class Collaborations Color Communication Communities Complex Computational Biology Computer software Condition Conflict (Psychology)Cues Culture Media Custom Cyclic AMP Data Data Analyses Demyelinating Diseases Dendrites Detection Development Differentiation and Growth Diffusion Dimensions Disease Disease model Distal Doctor of Philosophy Drug Delivery Systems Dyes Electrical Engineering Electron Microscopy Electronics Embryo Engineering Environment Enzymes Equipment Exposure to Faculty Feedback Fellowship Figs - dietary Fluorescence Flushing Funding Future Gene Cluster Gene Silencing Gene Targeting Generations Genes Genetic Genetic Techniques Genome Glass Goals Grant Graph Gray unit of radiation dose Green Fluorescent Proteins Growth Growth Cones Growth Factor Guanosine Triphosphate Phosphohydrolases Hand Head Healthcare Heating Hour Human Huntington Disease Hybrids Hydrogels Image Imagery Imaging Techniques Immobilization Incidence Incubators Individual Inflammatory Injury Institutes International Intervention Intestines Invasive Invertebrates Journals Knock-out Knowledge Label Lasers Lead Left Legal patent Length Lethal Genes Levamisole Libraries Life Life Expectancy Ligands Light Liquid substance Longevity Mainstreaming Mammals Maps Measurable Measurement Measures Mechanics Medicine Membrane Metals Methods Microfluidic Microchips Microfluidics Microspheres Microsurgery Mind Modeling Molecular Molecular and Cellular Biology Monitor Morphology Motion Motor Neuron Disease Motor Neurons Movement Mus Mutagenesis Mutation Myelin Nanotechnology Natural regeneration Nature Nematoda Nerve Nerve Degeneration Nerve Regeneration Nervous system structure Neurobiology Neurodegenerative Disorders Neuroglia Neurons New York Nobel Prize Noise Nuclear Numbers Operative Surgical Procedures Optics Organism Orthologous Gene Outcome Output Oxidopamine Oxygen Parkinson Disease Parkinsonian Disorders Pathway interactions Pattern Pattern Recognition Peripheral Nervous System Diseases Persons Phagocytosis Pharmaceutical Preparations Phenotype Phosphotransferases Physics Physiologic pulse Physiology Plasma Point Mutation Polyamines Population Positioning Attribute Preclinical Drug Evaluation Preparation Problem Solving Process Property Protein Overexpression Proteins Publications Pulse taking Purpose RNA Interference Rate Rattus Reader Reading Reagent Recovery Recruitment Activity Relative (related person)Reporting Reproducibility Reproduction Research Research Personnel Resistance Resolution Resources Resveratrol Right-On Risk Robotics Role Role playing therapy Running Scanning Science Scientist Score Screening procedure Sensory Series Shapes Side Signal Pathway Signal Transduction Silicon Smell Perception Solutions Son Sorting - Cell Movement Space Flight Speed Spinal Cord Staining method Stains Standards of Weights and Measures Stereotyping Stimulus Stroke Structure Students Study models Suction Surface Swimming Synapses System Systems Biology Techniques Technology Temperature Testing Therapeutic Intervention Thick Time Title Touch sensation Toxic effect Transfection Translations Traumatic Brain Injury Tube Uncertainty United States National Institutes of Health Universities Variant Vertebrates Wallerian Degeneration Week Work Yeasts Zebrafish absorption abstracting age group age related axon growth axon guidance axon regeneration axonopathy base behavior measurement career cell motility chemical release combinatorial computer science cost day density design desire disability dosage drug discovery drug testing experience fluorescence imaging functional genomics gain of function gene function gene interaction genetic manipulation high throughput screening high throughput technology human RTN4 protein human disease human embryonic stem cell image processing in vivo inhibitor/antagonist injured innovation insight instrumentation interest ionization killings knockout gene man mature animal medical schools microchip millisecond mortality motor neuron degeneration multi-photon mutant myelination nano nanolitre nanoparticle nanoscale nanosurgery nerve stem cell nervous system disorder neural growth neurodevelopment neuronal cell body neuronal growth neurotransmission neurotrophic factor news novel optical traps particle photonics prevent programs promoter protective effect prototype quantum receptor relating to nervous system release factor research study response satisfaction scaffold size small molecule stem cells success supercomputer synaptic function synaptogenesis transcriptional coactivator p75 translational medicine trend two-photon ultraviolet wound healing

项目摘要

In recent years, the advantages of using the nematode Caenorhabditis elegans as a model system for human disease have become increasingly apparent, culminating in two Nobel Prizes in Physiology and Medicine within the last five years. Existing vertebrate animal models, and the instrumentation incorporated to study them, cannot be utilized for high throughput assays for rapid identification of novel genes, and drug leads. The model organism C. elegans allows in vivo genome-wide assays and high- throughput screens due to the availability of unmatched genetic techniques, its transparency, and the ability to grow it in minute volumes. Yet, since the first publications in early 1960s, little has changed how scientists manipulate this tiny organism manually, as a result of which even simple large-scale assays still take months to years to complete. Importantly, due to the lack of key technologies, several assays either cannot be performed at all or have to be dramatically simplified for high-throughput screens. We propose (1) development of the first on-chip ultra high-throughput whole- animal manipulation technologies for in vivo drug screens and genome-wide discovery of gene functions and interactions by complex on-chip behavioral and biochemical assay strategies; and (2) the first large-scale in vivo study of mechanisms of neural degeneration and regeneration following reproducible injuries using the proposed techniques. The proposed technologies and high-throughput assay strategies can significantly impact discovery of many molecular mechanisms using disease models of small animals.

近年来，使用线虫秀丽隐杆线虫的优势随着人类疾病的模型系统变得越来越明显，最终达到在过去五年中，在生理学和医学方面的两个诺贝尔奖中。现存的脊椎动物模型以及用于研究它们的仪器，不能用于快速鉴定新基因和药物的高通量测定法铅。秀丽隐杆线虫模型允许体内基因组的分析和高由于无与伦比的遗传技术的可用性，吞吐量屏幕透明度以及以微量量生长的能力。但是，自第一批出版物以来在1960年代初，几乎没有改变科学家手动操纵这种微小的生物的方式，结果，即使是简单的大规模测定仍然需要数月到几年完全的。重要的是，由于缺乏关键技术，几种测定要么不能完全执行或必须大大简化用于高通量屏幕。我们提出（1）开发第一个芯片上超高通量的整体用于体内药物筛查和全基因组发现的动物操纵技术复杂的片上行为和生化测定的基因功能和相互作用策略；（2）关于神经机制的第一个大规模体内大规模研究使用拟议的可再现伤害后的退化和再生技术。拟议的技术和高通量测定策略可以使用疾病模型的许多分子机制的发现显着影响小动物。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High-throughput in vivo genetic and drug screening using femtosecond laser nano-surgery, and microfluidics.

使用飞秒激光纳米手术和微流体进行高通量体内遗传和药物筛选。

DOI：
10.1109/iembs.2008.4649743
发表时间：
2008
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
0
作者：
Rohde,Christopher;Gilleland,Cody;Samara,Chrysanthi;Zeng,Fei;Yanik,MehmetFatih
通讯作者：
Yanik,MehmetFatih

Organ-targeted high-throughput in vivo biologics screen identifies materials for RNA delivery.

DOI：
10.1039/c4ib00150h
发表时间：
2014-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
0
作者：
Chang TY;Shi P;Steinmeyer JD;Chatnuntawech I;Tillberg P;Love KT;Eimon PM;Anderson DG;Yanik MF
通讯作者：
Yanik MF

Microfluidic in vivo screen identifies compounds enhancing neuronal regeneration.

微流体体内筛选识别增强神经元再生的化合物。

DOI：
10.1109/iembs.2009.5334771
发表时间：
2009
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
0
作者：
Rohde,ChristopherB;Gilleland,Cody;Samara,Chrysanthi;Norton,Stephanie;Haggarty,Stephen;Yanik,MehmetFatih
通讯作者：
Yanik,MehmetFatih

High-throughput in vivo vertebrate screening.

DOI：
10.1038/nmeth.1481
发表时间：
2010-08
期刊：
NATURE METHODS
影响因子：
48
作者：
Pardo-Martin, Carlos;Chang, Tsung-Yao;Koo, Bryan Kyo;Gilleland, Cody L.;Wasserman, Steven C.;Yanik, Mehmet Fatih
通讯作者：
Yanik, Mehmet Fatih

High-throughput hyperdimensional vertebrate phenotyping.