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

基本信息

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
项目类别：
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

项目摘要

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）：“健康和疾病期间红细胞蛋白质组的变化”摘要：最近对红细胞（RBC）蛋白质组的研究已经产生了膜蛋白和可溶性蛋白的广泛列表。虽然这些红细胞蛋白质目录令人印象深刻，但它们几乎不包含任何定量信息。差异蛋白表达的分析对于发现和理解疾病的生物学基础、为诊断或预后提供新的生物标志物、评估风险状况和结果以及确定个体化治疗的新靶标至关重要。在过去的几年中，用于对复杂的肽混合物进行定量、比较分析的质谱法和软件取得了重大进展。我们假设红细胞中蛋白质的整体定量表达模式将反映正常生活中存在的差异以及因疾病而发生的差异。在这里，我们建议开发一个强大的、无标记的蛋白质组学平台，用于定义红细胞中的差异蛋白表达。我们将评估技术差异的水平，并定义由于个体间和性别差异而导致的差异。然后，我们将测试开发的平台，并应用它来定义两种经典红细胞疾病——阵发性睡眠性血红蛋白尿症（PNH）和钻石黑扇贫血症（DBA）——整体蛋白表达模式的差异。最后，我们将使用开发的平台和定义疾病的特征蛋白来监测疾病特异性治疗期间红细胞蛋白质组中发生的变化。我们的研究结果可能为这些疾病的病理生理学提供新的见解，并可能导致新标记物的鉴定，或发现用于开发诊断测试或药物的新靶点。此外，我们开发的工具应该广泛适用于不同生理或疾病状态的红细胞膜蛋白质组的定量比较。公共健康相关性：我们假设红细胞蛋白的整体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化。在这笔资助中，我们建议开发一个强大的、无标记的蛋白质组学平台，用于定义红细胞中的差异蛋白表达。我们将评估与平台相关的技术变化水平，并定义由于正常生理差异而导致的变化。然后，我们将测试开发的平台，应用它来定义两种经典红细胞疾病（即阵发性夜间血红蛋白尿症（PNH）和钻石黑扇贫血症（DBA））中发生的整体蛋白质表达模式的差异。我们的研究可能为这些疾病的病理生理学提供新的见解，并可能导致新标记的识别，或发现用于开发诊断测试或药物的新靶点。此外，我们开发的平台应该广泛适用于不同生理或疾病状态的红细胞蛋白质组的定量比较。