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脑白质异常，特别是髓鞘异常。该项目的前奏是在马其顿成功收集尸检大脑用于精神分裂症研究，在马其顿建立电子显微镜用于精神分裂症研究的成功合作，以及长期不断得到加强的信念，即髓鞘细微异常在精神分裂症中很重要。该项目由4个要素组成，每个要素都旨在促进我们对精神分裂症的了解，马其顿科学家的培训，以及马其顿重要的、可持续的科学能力。首先，我们建议使用电子显微镜测量白质中轴突及其髓鞘的大小，以确定这些在精神分裂症中是否异常，以及患有和不患有精神分裂症的人的年龄相关变化是否不同。这将使有抱负的马其顿科学家参与精神分裂症的研究，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。这将是体视学的一种新用途，由于组织体积的未知变化，体视学通常会避开密度测量，但这些困难是可以克服的。目前尚不清楚精神分裂症或正常衰老过程中脑白质的细胞成分发生了什么变化。我们已经在培训一名马其顿法医病理学家进行体视学方面的培训，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证明 精神分裂症中某些髓鞘相关蛋白或其mRNA的异常水平，但总的来说，只对最丰富的蛋白质进行了研究。蛋白质组学技术可以同时测量一块组织中的几乎所有蛋白质。我们将带来一名马其顿科学家开始分析样品，同时学习在哥伦比亚大学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，以在马其顿建立一个世界级的设施，那里的分析将继续，哥伦比亚设施主任的持续合作支持。第四，我们将把一位马其顿的信息学专家带到哥伦比亚基因组设施，在那里他将学习处理来自高通量rna测序(rna-seq)的原始数据，这将阐明我们样本中几乎所有mna物种的水平，他将培训马其顿的学生使用这些方法，这些方法具有广泛的生物学适用性。最终结果应该是马其顿在解决一个困难和重要问题方面发挥重要作用，以及至少四个用于研究和培训的核心设施。

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.