Three dimensional organisation and duplication of the eukaryotic basal body

真核基体的三维组织和复制

• 批准号: BB/I000402/1
• 负责人: Sue Vaughan
• 金额: $ 43.17万
• 依托单位: Oxford Brookes University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI000402%2F1
• 关键词: Three; dimensional; organisation; duplication; eukaryotic

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.

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。纤毛和鞭毛也作为细胞的天线来感知外部细胞环境。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。人们对基础体很感兴趣因为鞭毛和纤毛的组装缺陷以及基础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。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。导致非洲昏睡病的布氏锥虫和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。很明显，基底体对许多不同的细胞都是至关重要的，我们的工作旨在了解这种细胞器是如何复制的。电子显微镜向我们展示了这个细胞器结构的复杂性。一种叫做细胞电子断层扫描的技术现在让我们可以看到细胞的三维组织，这确实增强了我们对细胞生物学许多方面的理解。利用这种技术和其他显微镜方法，我们的目标首先是了解细胞中基底体的三维组织；其次，绘制基础体复制的每个组成部分的顺序，第三，研究参与基础体复制的基因的作用，以便深入了解这种复制过程是如何有序和调节的。

项目成果

A cell-body groove housing the new flagellum tip suggests an adaptation of cellular morphogenesis for parasitism in the bloodstream form of Trypanosoma brucei.

• DOI: 10.1242/jcs.139139
• 发表时间: 2013-12-15
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Hughes L;Towers K;Starborg T;Gull K;Vaughan S
• 通讯作者: Vaughan S

Patterns of organelle ontogeny through a cell cycle revealed by whole-cell reconstructions using 3D electron microscopy

使用 3D 电子显微镜进行全细胞重建揭示细胞周期中细胞器个体发育的模式

• DOI: 10.1242/dev.150045
• 发表时间: 2017
• 期刊: Development
• 影响因子: 4.6
• 作者: Hughes L

Cytokinesis in Trypanosoma brucei differs between bloodstream and tsetse trypomastigote forms: implications for microtubule-based morphogenesis and mutant analysis.

• DOI: 10.1111/mmi.12436
• 发表时间: 2013-12
• 期刊: Molecular microbiology
• 影响因子: 3.6
• 作者: Wheeler RJ;Scheumann N;Wickstead B;Gull K;Vaughan S
• 通讯作者: Vaughan S