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

描述(申请人提供)：了解大脑的结构和功能是一个突出的科学问题，神经退行性疾病是人类疾病中最昂贵、最具破坏性和最不好治疗的疾病之一，可以说是因为它们没有被很好地理解。阵列断层成像是一种新的组织成像方法，其三维分辨率足以分辨单个突触，并在大样本中提供多个(目前约40个)分子成分的定量表征。阵列断层成像数据使得能够在三维组织架构的背景下描述神经网络。我们相信，这些数据将使研究人员能够开始理解神经回路的正确功能，更重要的是，开始了解各种神经退化过程是如何存在和进展的。这一前景是诱人的，然而，由于方法的复杂性和在单个研究人员的实验室中建立它的成本，阵列断层扫描在2007年首次发表后被用于相对较少的研究(Micheva和Smith，2007)。Aratome已经成立，为研究界提供阵列断层扫描服务。我们相信，这是将该方法的力量应用于神经科学、癌症研究、医学诊断和治疗发展中的问题的最佳方式。为此，在本申请中，我们建议将阵列生产中最脆弱的方面工业化，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：随着人口老龄化，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。由于缺乏对疾病过程的基本了解，开发这些疾病的治疗方法的努力一直受到阻碍，部分原因是缺乏提供有关疾病进展的“全景”信息的技术。我们建议开发一种对大脑进行高分辨率蛋白质组分析的技术，以更好地了解病理，使未来能够开发更有效的治疗方法。

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.