CHANGES IN THE RBC PROTEOME DURING HEALTH AND DISEASE

健康和疾病期间红细胞蛋白质组的变化

• 批准号: 7887839
• 负责人: Monica Bessler
• 金额: $ 42.78万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7887839
• 关键词: Acquired Hemolytic Anemia; Age; Bioinformatics; Biological; Biological Markers; Cancer Center; Cataloging; Catalogs; Cell membrane; Collaborations; Complement; Complement component C5; Complex Mixtures; Computer Analysis; Computer software; Core Facility; Coupled; Cyclotrons; Cytolysis; Data; Detection; Development; Diagnosis; Diagnostic tests; Diamond-Blackfan anemia; Disease; Dose; Erythrocytes; Erythroid; Erythroid Cells; Female; Fourier Transform; Functional disorder; Gender; Goals; Grant; Health; Individual; Individual Differences; Inherited; Investigation; Ions; Label; Lead; Life; Maintenance; Mass Spectrum Analysis; Measures; Mediating; Membrane; Methods; Modeling; Molecular; Molecular Profiling; Monitor; NIH Program Announcements; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Patients; Pattern; Peptides; Pharmaceutical Preparations; Physiological; Preparation; Proteins; Proteome; Proteomics; Race; Research; Risk; Running; Sampling; Sex Characteristics; Steroids; Testing; Time; Universities; Variant; Washington; abstracting; capillary liquid chromatography; comparative; computerized data processing; density; inhibitor/antagonist; insight; instrument; male; mass spectrometer; nano; novel; novel marker; outcome forecast; protein expression; public health relevance; rat Piga protein; response; tool

DESCRIPTION (provided by applicant): "Changes in the RBC proteome during health and disease" Abstract: Recent studies of the red blood cell (RBC) proteome have yielded extensive lists of both membrane and soluble proteins. While these catalogs of RBC proteins are quite impressive, they contain little if any quantitative information. The analysis of differential protein expression can be crucial for the discovery and understanding of the biological underpinnings of disease, as well as for providing novel biomarkers for diagnosis or prognosis, for assessing risk profiles and outcomes, and for identifying novel targets for individualized treatment. Within the last few years there have been significant advances in mass spectrometry and software for the quantitative, comparative analysis of complex mixtures of peptides. We hypothesize that the global quantitative expression patterns of proteins in RBC will reflect differences that exist in normal live but also those that occur due to disease. Here we propose to develop a robust, label-free proteomics platform for defining differential protein expression in RBCs. We will assess the level of technical variation, as well as define variations due to inter-individual and gender differences. We will then test the platform developed and apply it to define the differences in global protein expression patterns in two classic red blood cell disorders, Paroxysmal Nocturnal Hemoglobinuria (PNH) and Diamond Blackfan Anemia (DBA). Finally, we will use the platform developed and the signature proteins that define the disease to monitor the changes that occur in the RBC proteome during disease specific treatment. Our findings are likely to provide new insights into the pathophysiology of these diseases, and might lead to the identification of novel markers, or to the discovery of new targets for the development of diagnostic tests or drugs. Furthermore, the tools we develop should prove broadly applicable to the quantitative comparison of RBC membrane proteomes of varying physiological or disease states. PUBLIC HEALTH RELEVANCE: We hypothesize that the global quantitative expression patterns of red cell proteins will reflect normal physiological variations, as well as variations that occur during disease. In this grant we propose to develop a robust, label-free proteomics platform for defining differential protein expression in red blood cells. We will assess the level of technical variation associated with the platform and define variations due to normal physiological differences. We will then test the developed platform by applying it to define the differences in global protein expression patterns that occur in two classic red blood cell disorders, namely Paroxysmal Nocturnal Hemoglobinuria (PNH) and Diamond Blackfan Anemia (DBA). Our investigations are likely to provide new insights into the pathophysiology of these diseases, and might lead to the identification of novel markers, or to the discovery of new targets for the development of diagnostic tests or drugs. Furthermore, the platform we develop should prove broadly applicable to the quantitative comparison of RBC proteomes of varying physiological or disease states.

描述（由申请人提供）：“健康和疾病期间RBC蛋白质组的变化”摘要：对红细胞（RBC）蛋白质组的最新研究已经获得了膜和可溶性蛋白的广泛清单。尽管这些RBC蛋白的目录令人印象深刻，但它们几乎没有定量信息。差异蛋白表达的分析对于发现和理解疾病生物基础以及为评估诊断或预后的新型生物标志物，评估风险特征和结果以及确定新颖的个性化治疗目标至关重要。在过去的几年中，质谱和软件在定量，比较肽的比较分析方面取得了重大进展。我们假设RBC中蛋白质的全球定量表达模式将反映正常现场存在的差异，也反映出由于疾病而发生的差异。在这里，我们建议开发一个可靠的，无标签的蛋白质组学平台，用于定义RBC中的差异蛋白表达。我们将评估技术差异的水平，并根据个人间差异和性别差异定义变化。然后，我们将测试开发的平台，并将其应用以定义两种经典的红细胞疾病，阵发性夜间夜间血红蛋白尿（PNH）和钻石黑芬贫血（DBA）中全球蛋白质表达模式的差异。最后，我们将使用开发的平台和定义疾病的签名蛋白来监测疾病特定治疗过程中RBC蛋白质组中发生的变化。我们的发现很可能为这些疾病的病理生理学提供新的见解，并可能导致对新标记的鉴定，或者发现发现诊断检查或药物开发的新靶标。此外，我们开发的工具应广泛地适用于不同生理或疾病状态的RBC膜蛋白质组的定量比较。 公共卫生相关性：我们假设红细胞蛋白的全球定量表达模式将反映正常的生理变化以及疾病期间发生的变异。在这笔赠款中，我们建议开发一个稳健的无标签蛋白质组学平台，用于定义红细胞中差异蛋白的表达。我们将评估与平台相关的技术变化水平，并因正常的生理差异而定义变化。然后，我们将通过应用它来定义在两种经典的红细胞疾病中发生的全球蛋白质表达模式的差异来测试开发的平台，即阵发性夜间夜间血红蛋白尿（PNH）和钻石黑芬芳基（Damond Blackfan）（DBA）。我们的研究可能会提供对这些疾病的病理生理学的新见解，并可能导致鉴定新标记物，或发现发现开发诊断检查或药物的新靶标。此外，我们开发的平台应广泛地适用于不同生理或疾病状态的RBC蛋白质组的定量比较。