New proteome techniques: mapping adult D. Melanogaster

新蛋白质组技术：绘制成年黑腹果蝇图谱

• 批准号: 9009178
• 负责人: DAVID E. CLEMMER
• 金额: $ 25.41万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-22 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9009178
• 关键词: Adult; Age; Alzheimer' s Disease; Animals; Antibodies; Area; Beds; Biological; Biological Markers; Biological Models; Brain; Central Nervous System Diseases; Cessation of life; Comb animal structure; Complex; Complex Mixtures; DNA Sequence Alteration; Detection; Development; Dimensions; Disease Progression; Disease model; Drosophila genus; Drosophila melanogaster; Fluorescence; Gases; Gene Expression; Genes; Genome; Genotype; Human; Huntington Disease; Individual; Ions; Isomerism; Label; Liquid Chromatography; Longevity; Maps; Mass Spectrum Analysis; Measurement; Measures; Modeling; Molecular; Molecular Chaperones; Monitor; Nature; Nerve Degeneration; Onset of illness; Organism; Parkinson Disease; Pathway interactions; Peptides; Phase; Physiological; Polysaccharides; Population; Population Analysis; Population Control; Positioning Attribute; Program Development; Protein Conformation; Protein Isoforms; Proteins; Proteome; Proteomics; Reproducibility; Research; Resolution; Sampling; Source; Spectrometry; Speed; Structure; Study models; System; Techniques; Technology; Temperature; Testing; Time; Transgenic Organisms; Tube; Validation; Work; age related; analytical method; comparative; electric field; genetic strain; genetic variant; high throughput analysis; improved; instrument; instrumentation; ion mobility; molecular phenotype; mutant; new technology; next generation; novel; parkin gene/protein; protein complex; protein expression; public health relevance; research study; small molecule; synuclein; tool; two-dimensional

 DESCRIPTION (provided by applicant): A problem of biomarker discovery efforts is that current analytical methods do not have the capacity to analyze in a timely manner the numerous molecular species within complex biological samples. This problem is exacerbated by the fact that many different samples must be analyzed in order to establish the normal variability across a population for any given molecular species. Here we propose the development of a new analytical instrument that utilizes rapid, gas-phase separations to increase the overall experimental throughput by more than an order of magnitude. The new instrumentation will employ multidimensional ion mobility spectrometry (IMS) techniques to obtain the rapid analysis. By using two dimensions of IMS separations and changing operational parameters such as the electric field and measurement temperature it is anticipated that peak capacities (prior to mass spectrometric analysis) in excess of 104 will be obtained. This is remarkable because it is larger than that obtained from two-dimensional liquid chromatography (LC) separations and requires a fraction of the time. The new instrumentation will be used to characterize the D. melanogaster proteome at different times in the organism lifespan. The significantly increased throughput will allow comparisons of individual organisms with the population mean to better group organisms according to molecular phenotype. Additionally, a novel fluorescent labeling strategy will be employed to better compare the physiological age of individual organisms as opposed to chronological age. The measurement platform will be applied to transgenic Parkinson's and Alzheimer's disease Drosophila in order to determine molecular changes associated with disease progression.