Three dimensional organisation and duplication of the eukaryotic basal body

人体内几乎所有的细胞都含有一个叫做中心粒或基底体的细胞器，它具有多种功能。它在组织有丝分裂纺锤体方面很重要，当细胞分裂时，有丝分裂纺锤体分离染色体。它组装了一种称为纤毛或鞭毛的结构，允许精子细胞等细胞移动，纤毛存在于肺部衬里的细胞中，在那里它们帮助液体的移动。纤毛和鞭毛也充当细胞的触角，以感知外部细胞环境。大多数生物体含有纤毛或鞭毛，它们对许多不同的单细胞生物体的运动以及细胞附着在表面上都是重要的。由于鞭毛和纤毛的组装缺陷和基底体的复制缺陷与一系列人类疾病有关，这些疾病统称为纤毛病，因此人们对基底体非常感兴趣。这些疾病包括多囊肾病、视网膜变性、Kartag‘s综合征、Bardet-Biedl综合征。例如，后两种疾病与多种病理因素有关，如慢性支气管炎、男性不育症、肥胖症和糖尿病。这一系列令人眼花缭乱的病理现象，部分是由于人体基础身体的许多功能所致。引起非洲昏睡病的布鲁氏锥虫和在南美洲引起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鞭毛的组装和功能，是研究人员正在研究的主要致病因素。很明显，基底体对于许多不同的细胞是至关重要的，我们的工作旨在了解这个细胞器是如何复制的。电子显微镜向我们展示了这种细胞器的结构复杂性。一种名为细胞电子断层扫描的技术现在使我们能够可视化细胞的三维组织，这确实增强了我们对细胞生物学许多方面的理解。利用这项技术和其他显微镜方法，我们的目标是首先了解细胞中基底的三维组织；其次绘制基底的每个组成部分复制的顺序；第三，研究参与基底复制的基因的作用，以便深入了解这种复制过程是如何排序和调节的。

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 and flagella also acts as the cells antenna 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 lot 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 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. It is clear that basal bodies are crucial for many different cells and our work is aimed at understanding how this organelle duplicates. Electron microscopy has shown us the structural complexity of this organelle. A technique called cellular electron tomography is now allowing us to visualise the three dimensional organisation of cells and this is really enhancing our understanding of many aspects of cell biology. Using this technique and other microscopy approaches we aim firstly to understand the three dimensional organisation of basal bodies in cells; secondly to map the order with which each component of the basal body duplicates and, thirdly investigate role of genes that are involved in basal body duplication in order to gain insights into how this duplication process is ordered and regulated.