Automating Array Production for High-resolution Three-dimensional Proteomic Imagi

自动化阵列生产高分辨率三维蛋白质组图像

• 批准号: 8394524
• 负责人: JAY K TRAUTMAN
• 金额: $ 23.52万
• 依托单位: ARATOME, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8394524
• 关键词: Affinity; Age; Alzheimer' s Disease; Amines; Antibodies; Architecture; Biological Neural Networks; Brain; Carbon; Chemicals; Communities; Coupling; Data; Data Quality; Defect; Deposition; Development; Devices; Diagnostic; Diazomethane; Dimensions; Disease; Disease Progression; Due Process; Electron Microscopy; Failure; Film; Fluorescence; Future; Gelatin; Human; Image; Individual; Industrialization; Intervention; Lasers; Length; Lifting; Link; Mechanics; Medical; Methods; Molecular; Nerve Degeneration; Neurodegenerative Disorders; Neurosciences; Parkinson Disease; Pathology; Population; Positioning Attribute; Preparation; Price; Procedures; Process; Production; Proteomics; Publications; Publishing; RNA Splicing; Research; Research Personnel; Resolution; Robotics; Sampling; Scanning Electron Microscopy; Scheme; Services; Silanes; Speed; Staining method; Stains; Structure; Surface; Synapses; Technology; Time; Tissue Embedding; Tissues; Ursidae Family; Water; anticancer research; arm; carboxyl group; cost; crosslink; design; effective therapy; fluorescence imaging; fluorescence microscope; functional group; meetings; neural circuit; operation; prototype; silane; therapeutic development; tomography; vapor

DESCRIPTION (provided by applicant): Understanding the structure and function of the brain is an outstanding scientific problem, and neurodegenerative diseases are among the most expensive, disruptive, and least well treated of human maladies, arguably because they are not well understood. Array Tomography is a new method for tissue imaging with resolution in all three dimensions sufficient to resolve individual synapses and provide quantitative characterization of multiple (currently ~40) molecular constituents, throughout large samples. Array Tomography imaging data enables the description of neural networks in the context of the three-dimensional tissue architecture. We believe such data will enable researchers to begin to comprehend the proper function of neural circuits and, importantly, to begin to understand how it is that the various neurodegenerative processes present and progress. This prospect is alluring, and yet, due to the complexity of the method and the cost of establishing it in the lab of an individual investigator, Array Tomography has been used in relatively few studies following the first publication in 2007 (Micheva and Smith, 2007). Aratome has been established to offer Array Tomography as a service to the research community. We believe this is the best way to bring the power of the method to bear on problems in neuroscience, cancer research, medical diagnostics and therapeutics development. To that end, in this application we propose to industrialize the most fragile aspects of array production, which will reduce the cost of producing high quality data and allow an offering at a commercially viable price. PUBLIC HEALTH RELEVANCE: Neurodegenerative diseases, including Alzheimer's and Parkinson's, are becoming increasingly prevalent as the population ages. Efforts to develop treatments for these diseases have been hampered by a lack of basic understanding of the disease processes, due in part to the lack of technologies that provide "big picture" information regarding the disease progression. We propose to develop a technology for high-resolution proteomic analysis of the brain to better understand the pathologies, enabling the development of more effective treatments in the future.

描述（由申请人提供）：了解大脑的结构和功能是一个杰出的科学问题，而神经退行性疾病是对人类疾病的最昂贵，最颠覆性且最不受治疗的疾病之一，这可以说是因为它们没有得到充分的理解。阵列断层扫描是一种在所有三个维度的分辨率的组织成像的新方法，足以解析单个突触并在整个大型样品中提供多种（当前〜40）分子成分的定量表征。阵列断层扫描成像数据可以在三维组织结构的上下文中描述神经网络。我们认为，这样的数据将使研究人员能够开始理解神经回路的正确功能，并重要的是，开始了解各种神经退行性过程的存在和进步。这种前景诱人，但是，由于该方法的复杂性和在个人研究者实验室中建立它的成本，阵列层析成像在2007年第一次出版物之后相对较少的研究中使用了（Micheva和Smith，2007年）。已经建立了Aratome，以提供阵列层析成像作为研究社区的服务。我们认为，这是赋予该方法解决神经科学，癌症研究，医学诊断和治疗性开发问题的最佳方法。为此，在此应用中，我们建议将阵列生产最脆弱的方面产生工业化，这将降低生产成本 高质量的数据，并允许以商业上可行的价格提供产品。 公共卫生相关性：随着人口年龄的增长，包括阿尔茨海默氏症和帕金森氏症在内的神经退行性疾病正变得越来越普遍。缺乏对疾病过程的基本了解，妨碍了为这些疾病开发治疗的努力，部分原因是缺乏提供有关疾病进展的“大局”信息的技术。我们建议开发一种用于对大脑的高分辨率蛋白质组学分析的技术，以更好地了解病理，从而在将来开发更有效的治疗方法。