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2007 NIH Director's Pioneer Award Program (DP1)

2007 NIH 院长先锋奖计划 (DP1)

基本信息

批准号：
7665381
负责人：
RUSTEM F ISMAGILOV
金额：
$ 76.75万
依托单位：
UNIVERSITY OF CHICAGO
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 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7665381
关键词：
Achievement Address Affect Age Aging Aging-Related Process Air Alzheimer&apos s Disease Animal Model Antibodies Area Award Axon Behavior Behavioral Benign Binding Biochemical Biochemical Reaction Biological Biological Assay Biological Neural Networks Biology Biomedical Research Blood Clot Blood coagulation Brain Caenorhabditis elegans Cell Culture Techniques Cell Death Cells Chemical Stimulation Chemicals Chemistry Chicago Chimeric Proteins Coagulation Process Cognitive Communities Complex Crystallization Data Development Devices Diagnosis Diagnostic Diffusion Discipline Disease Disease Progression Disease model Drosophila genus Electrodes Elements Embryo Embryonic Development Engineering Environment Equilibrium Event Exhibits Fellowship Field Flow Fractionation Figs - dietary Fluorescence Foundations Generations Genes Genetic Polymorphism Genomics Goals Grant Growth Hand Heat-Shock Response Hemostatic function Human Huntington Disease In Vitro Individual Injection of therapeutic agent Institution Insulin Investigation Ion Channel Ions Kinetics Knowledge Laboratories Lead Learning Life Link Lipids Liquid substance Longevity Mathematics Measures Mechanical Stimulation Mediating Membrane Membrane Lipids Membrane Proteins Memory Metals Methods Microfluidic Microchips Microfluidics Miniaturization Modeling Molecular Molecular Chaperones Monitor Morphology Nature Nerve Degeneration Neurodegenerative Disorders Neurons Neurosciences Non-Insulin-Dependent Diabetes Mellitus Organism Oxidants Pacemakers Paralysed Parkinson Disease Pathway interactions Pattern Peptide Hydrolases Pharmaceutical Preparations Pharmacologic Substance Phenotype Phosphoric Monoester Hydrolases Phosphotransferases Physics Physiological Plasma Plug-in Positioning Attribute Prions Probability Procedures Process Proteins Proteolysis Publications RNA Interference Reaction Reactive Oxygen Species Reagent Recording of previous events Relative (related person)Research Research Personnel Research Project Grants Resolution Resources Rest Risk Sampling Science Scientist Screening procedure Signal Pathway Slice Smell Perception Societies Solutions Spatial Distribution Staging Stochastic Processes Stream Stress Structure Surface Symptoms Synapses System Techniques Technology Technology Transfer Temperature Testing Thioflavin T Thromboplastin Time Tissue Model Tissues Touch sensation Toxic effect United States National Institutes of Health Variant Water Work age effect aged animal tissue base beta pleated sheet career cytotoxicity data acquisition design disease diagnosis drug candidate effective therapy excitotoxicity experience extracellular high risk human DICER1 protein human disease in vitro Assay in vivo innovation insight interdisciplinary approach interest interfacial knowledge base millisecond monomer mutant neutrophil novel diagnostics optical imaging oxidation prevent professor programs protein aggregate protein aggregation protein misfolding prototype quantum receptor research study response single molecule small molecule spatiotemporal technology development tool tool development

项目摘要

This proposal describes a multi-disciplinary research program that aims to develop, validate, and disseminate microfluidic technologies for quantitative studies of protein aggregation and aging. Protein aggregation is associated with aging and with a number of human diseases that affect both quality and duration of life. Many fundamental aspects of protein aggregation remain elusive, including connections between protein aggregation and toxicity, and the connection between protein aggregation and initiation and progression of diseases. Microfluidic platforms will be developed to understand these complex processes from both bottom-up and top-down perspectives. Bottom-up, new droplet-based microfluidic systems will be developed to characterize quantitatively the connection between protein aggregation and toxicity in vitro. This system will allow the reproducible real-time generation, manipulation, and characterization of aggregates for in vitro and in vivo toxicity screens. Multidimensional statistical analysis of toxicity patterns obtained in these devices may elucidate the connection between protein aggregation and toxicity, clarify the mechanism of action of existing drug candidates that target aggregation, and accelerate development of new drugs and drug cocktails. Top-down, microfluidic technologies will be developed to induce and monitor aggregation in vivo with high spatiotemporal resolution, and to observe the effects of aging, physiological state, neuronal activity, and presence of drug candidates on the initiation and progression of protein aggregation diseases. These two technologies will be used together to understand protein aggregation and aging, and may lead to new hypothesis and molecules for controlling these processes.

该提案描述了一个多学科的研究计划，旨在开发、验证和推广微流体技术，蛋白质聚集和衰老的研究。蛋白质聚集与老化和一些影响质量和持续时间的人类疾病生命蛋白质聚集的许多基本方面仍然难以捉摸，包括蛋白质聚集和毒性之间的联系，蛋白质聚集和蛋白质聚集的起始和进展之间的联系疾病微流体平台将被开发来理解这些复杂的从自下而上和自上而下两个角度进行分析。自下而上，全新将开发基于液滴的微流控系统，定量研究了蛋白质聚集与体外毒性之间的关系。该系统将允许可再现的实时生成、操作和用于体外和体内毒性筛选的聚集体的表征。对这些器械中获得的毒性模式进行多维统计分析可以阐明蛋白质聚集和毒性之间的联系，澄清靶向聚集的现有候选药物的作用机制，以及加快新药和鸡尾酒药物的开发。自上而下，微流体将开发诱导和监测体内聚集的技术，高时空分辨率，并观察衰老，生理状态、神经元活性和起始时候选药物的存在，蛋白质聚集疾病的进展。这两项技术将在一起使用，以了解蛋白质聚集和老化，并可能导致新的控制这些过程的假说和分子。