Building Schizophrenia Research in Macedonia

描述（由申请人提供）：我们建议纽约的哥伦比亚大学和斯科普里的马其顿科学与艺术学院合作，研究精神分裂症患者的大脑白色物质，特别是髓鞘的异常。该项目的前奏是在马其顿成功合作收集尸检大脑用于精神分裂症的研究，在马其顿成功合作建立电子显微镜用于精神分裂症的研究，以及长期以来不断得到加强的信念，即髓鞘的细微异常在精神分裂症中很重要。该项目由4个要素组成，每个要素都旨在提高我们对精神分裂症的认识，培训马其顿科学家，以及在马其顿建立重要的可持续科学能力。首先，我们建议使用电子显微镜来测量轴突的大小和它们的髓鞘在白色物质，以确定这些是否是异常的精神分裂症，以及是否年龄相关的变化是不同的人与精神分裂症。这将使有抱负的马其顿科学家参与精神分裂症研究，并将巩固我们的电子显微镜设施作为国家资源的作用。其次，我们建议使用体视学来确定白色物质中少突胶质细胞和小胶质细胞的密度。这将是体视学的一个新用途，由于组织体积的未知变化，体视学通常避免测量密度，但这些困难是可以克服的。目前还不清楚精神分裂症或正常衰老过程中白色物质的细胞组成发生了什么变化。我们已经在对一名马其顿法医病理学家进行体视学培训，该项目将支持一个他可以培训其他人的设施。第三，我们和其他人有强有力的证据， 精神分裂症中某些髓鞘相关蛋白或其mRNA的异常水平，但一般而言，仅研究了最丰富的蛋白。蛋白质组学技术可以同时测量一块组织中的所有蛋白质。我们将邀请一位马其顿科学家来开始分析样本，同时学习在哥伦比亚的核心设施中使用最先进的无标记蛋白质组学，之后马其顿科学部将支持购买类似的仪器，在马其顿建立一个世界级的设施，在那里分析将继续进行，并继续得到哥伦比亚设施主任的合作支持。第四，我们将邀请一位马其顿的信息学专家到哥伦比亚基因组研究所，他将学习如何处理高通量RNA测序（RNA-seq）的原始数据，这些数据将阐明我们样本中几乎所有mRNA种类的水平，他将培训马其顿的学生使用这些具有广泛生物适用性的方法。最后的结果应该是马其顿在解决一个困难和重要的问题方面发挥主要作用，并至少有四个核心研究和培训设施。

DESCRIPTION (provided by applicant): We propose a collaboration between Columbia University, in New York, and the Macedonian Academy of Sciences and Arts, in Skopje, to investigate abnormalities of cerebral white matter, and particularly myelin, in schizophrenia. The preludes to this project are a successful collaboration to collect autopsy brains in Macedonia for research on schizophrenia, a successful collaboration to establish electron microscopy in Macedonia for the study of schizophrenia, and a longstanding conviction, continually receiving reinforcement, that subtle abnormalities of myelin are important in schizophrenia. The project consists of 4 elements, each designed to advance our knowledge of schizophrenia, the training of Macedonian scientists, and an important, sustainable scientific capability in Macedonia. First, we propose to use electron microscopy to measure the sizes of axons and their myelin sheaths in the white matter, in order to determine whether these are abnormal in schizophrenia, and whether age-related changes are different in people with and without schizophrenia. This will involve aspiring Macedonian scientists in schizophrenia research and will solidify the role of our electron microscopy facility as a national resource. Second, we propose to use stereology to determine densities of oligodendrocytes and microglia in white matter. This will be a novel use of stereology, which generally shuns the measurement of densities because of unknown changes in tissue volumes, but these difficulties can be overcome. It is not clearly known what changes in the cellular composition of white matter take place in schizophrenia or in normal aging. We are already training a Macedonian forensic pathologist in stereology, and the project will support a facility in which he can train others. Third, we and others have strong evidence for abnormal levels of certain myelin-related proteins or their mRNA in schizophrenia, but in general, only the most abundant proteins have been investigated. Proteomic techniques exist that can measure essentially all proteins in a piece of tissue simultaneously. We will bring a Macedonian scientist to begin to analyze samples while learning to use state-of-the-art label-free proteomics in the core facility at Columbia, after which the Ministry of Science in Macedonia will support the purchase of similar instrumentation to establish a world-class facility in the Macedonia, where analysis will continue, with continued collaborative support from the director of the facility at Columbia. Fourth, we will bring a Macedonian expert in informatics to the Columbia genome facility, where he will learn to process raw data from high-throughput RNA sequencing (RNA-seq) that will elucidate levels of essentially all mRNA species in our samples, and he will train students in Macedonia in these methods, which have wide biological applicability. The final outcome should be a major role for Macedonia in solving a difficult and important problem, and at least four core facilities for research and training.