Quantitative Proteome Analysis of Brain Development

大脑发育的定量蛋白质组分析

• 批准号: 7469740
• 负责人: John R Yates III
• 金额: $ 42.64万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7469740
• 关键词: American; Animal Model; Animals; Anions; Arts; Beds; Behavior; Behavioral; Biological; Brain; Brain region; Caliber; Cations; Collaborations; Complex; Computer software; Data; Databases; Development; Disease; Dissociation; Electron Transport; Functional disorder; Goals; Grant; Health; High Pressure Liquid Chromatography; Ion Exchange; Ions; Label; Life; Liquid Chromatography; Liquid substance; Mass Spectrum Analysis; Measures; Mental Depression; Metabolic; Methods; Molecular; Monitor; Mood Disorders; Phase; Phenotype; Phosphopeptides; Phosphoproteins; Phosphorylation; Population; Probability; Process; Protein Analysis; Proteins; Proteome; Proteomics; Psychotic Disorders; Public Health; Range; Rattus; Reaction; Research; Resolution; Rodent; Schizophrenia; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Site; Software Tools; Symptoms; System; Techniques; Technology; Therapeutic; Tissues; Tubular formation; Western Blotting; brain tissue; data acquisition; data mining; improved; particle; software development; tandem mass spectrometry; tool; ultra high pressure

DESCRIPTION (provided by applicant): Our overall objective is to develop and exploit 15N labeling of rats for quantitative global analysis of signal transduction pathways in the brain. Signal transduction is a key elicitor of a diverse array of functions in the brain that impacts different behaviors. Technology to analyze 15N labeled rat brain proteins to determine quantitative changes in protein phosphorylation provides a means to globally study the activation or suppression of signaling pathways. The ability to perform these studies on discrete sections of the brain will allow the study of brain regions believed to be important in specific behavioral phenotypes. In this project, we will develop the means to quantitatively measure protein phosphorylation in discrete regions of the rat brain using animal models of schizophrenia. Our hypothesis is 15N metabolic labeling of rodents can be used to study signal transduction processes involved in brain dysfunction. The long term goal is to develop methods and technologies to study affective disorders, a health issue for roughly 20 million Americans (5-7% of the population). PUBLIC HEALTH RELEVANCE: Approximately, 20 million Americans are stricken with affective disorders of some type. This research will help establish approaches for examining the molecular processes associated with these disorders. A fundamental understanding of these processes will help the development of therapeutics to alleviate the symptoms associated with affective disorders such as schizophrenia, psychosis, biopolar disorder, and depression.

描述（由申请人提供）：我们的总体目标是开发和利用大鼠的15N标记，以定量大脑信号转导途径的全局分析。信号转导是影响不同行为的大脑功能各种功能的关键引起者。分析15N标记大鼠脑蛋白以确定蛋白质磷酸化的定量变化的技术为全球研究信号通路的激活或抑制提供了一种手段。对大脑离散部分进行这些研究的能力将允许对被认为在特定行为表型中很重要的大脑区域进行研究。在该项目中，我们将使用精神分裂症的动物模型来定量测量大鼠脑离散区域的蛋白质磷酸化的手段。我们的假设是啮齿动物的15N代谢标记可用于研究涉及脑功能障碍的信号转导过程。长期目标是开发研究情感障碍的方法和技术，这是大约2000万美国人（占人口的5-7％）的健康问题。公共卫生相关性：大约有2000万美国人遭受某种类型的情感障碍。这项研究将有助于建立检查与这些疾病相关的分子过程的方法。对这些过程的基本理解将有助于发展治疗剂，以减轻与精神分裂症，精神病，生物极度障碍和抑郁症等情感障碍相关的症状。