Using SBEM and cellular electron tomography to study the basal body/pro-basal body linker.

人体中几乎所有的细胞都含有一种细胞器，称为中心粒或基体，具有多种功能。它在组织有丝分裂纺锤体中很重要，当细胞分裂时，纺锤体分离染色体。它组装了一种叫做纤毛或鞭毛的结构，这种结构允许精子细胞等细胞移动，而纤毛存在于肺内壁的细胞中，在那里它们帮助液体运动。纤毛是人体细胞感知外部细胞环境的天线。大多数生物都含有纤毛或鞭毛，它们对许多不同的单细胞生物的运动很重要，也允许细胞附着在表面上。人们对基础体非常感兴趣因为鞭毛和纤毛的组装缺陷和基础体的复制缺陷与一系列统称为纤毛病的人类疾病有关。这些疾病包括多囊肾病、视网膜变性、Kartagener综合征、Bardet-Biedl综合征。例如，后两种疾病与多种病理有关，如慢性支气管炎、男性不育、肥胖和糖尿病。这种令人眼花缭乱的病理阵列部分是由于人体中基底体的许多功能。导致非洲昏睡病和牛那加纳病的布氏锥虫、导致南美恰加斯病的克氏锥虫以及疟疾寄生虫疟原虫等寄生生物都依赖于鞭毛的组装和功能，这是研究人员正在研究的一个主要毒力因素。基底体是细胞中的小细胞器，电子显微镜是向我们展示这种细胞器结构复杂性的必要手段。三维显微术最近取得了一些进展，它帮助生物学家了解细胞空间组织的许多方面。两种被称为连续块面扫描电子显微镜和阵列断层扫描的新技术使生物学家第一次能够重建单个细胞和大面积组织（如大脑中的突触连接）的三维视图。这笔拨款的一部分用于使用这些新技术，开发我们可以收集和分析大型数据集的方法。

Nearly all cells in the human body contain an organelle called a centriole or basal body which has multiple functions. It is important in organising the mitotic spindle that segregates chromosomes when cells divide. It assembles a structure called a cilium or flagellum that allow cells such as sperm cells to move and cilia are found in cells in the lining of the lungs where they aid the movement of liquids. Cilia are the antenna of cells in Humans to sense the external cellular environment. Most organisms contain cilia or flagella and they are important for locomotion in many diverse single celled organisms as well as allowing cells to attach to surfaces. There is a great deal of interest in basal bodies because defects in the assembly of flagella and cilia and defects in duplication of basal bodies have been implicated in a range of human diseases that are collectively called the ciliopathies. These diseases include polycystic kidney disease, retinal degeneration, Kartagener's syndrome, Bardet-Biedl syndrome. These latter two diseases, for example are associated with a broad spectrum of pathologies, such as chronic bronchitis, male sterility, obesity and diabetes.This bewildering array of pathologies is due, in part, to the many functions of basal bodies in the human body. Parasitic organisms such as Trypanosoma brucei which causes African sleeping sickness and Nagana in cattle, Trypanosoma cruzi, which causes Chagas disease in South America, as well as the malaria parasite Plasmodium all rely on the assembly and function of a flagellum and is a major virulence factor that is being investigated by researchers.Basal bodies are small organelles in cells and electron microscopy is necessary to show us the structural complexity of this organelle. There have been recent developments in three dimensional microscopy which helps biologists to understand many aspects of the spatial organisation of cells. Two new techniques called serial block face scanning electron microscopy and array tomography are allowing biologists, for the first time, to reconstruct three dimensional views of individual cells and large areas of tissue such as synapse connections in the brain. Part of this grant to to work with these new techniques and develop ways in which we can gather and analyse large data sets.