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Understanding the inheritance of the Endoplasmic Reticulum during cell division

了解细胞分裂过程中内质网的遗传

基本信息

批准号：
1618887
负责人：
金额：
--
依托单位：
King's College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1618887
关键词：
Understanding inheritance Endoplasmic Reticulum during

项目摘要

Strategic Research Priority: World Class BioscienceAbstract Division requires the precise segregation of the entire set of cellular structures. Despite this, studies of eukaryotic cell division have tended to focus on chromosomes segregation, while almost nothing is known about the way the ER is segregated at division. The aim of this project is to use advanced imaging technologies and biophysical techniques to remedy this to understand how the endoplasmic reticulum is properly formed and distributed between daughter cells during mitosis and divisions. Project The endoplasmic reticulum (ER) is a network of internal membranes that is continuous with the nuclear envelope, and that extends through the cytoplasm of all eukaryotic cells. Despite its importance, the mechanisms controlling the proper inheritance of this organelle at division remain largely unknown. During cell division, the ER must be remodelled, partitioned into daughter cells and reassembled into both a functional ER and a sealed nuclear envelope. The purpose of this PhD will be to characterize roles played by the cytoskeleton and a recently described membrane trafficking machinery called ESCRT, in ER shaping and inheritance, processes essential for proper organelle biogenesis. ESCRT is an ideal target for this analysis since it plays important roles in cytokinesis and endosomal sorting2. Moreover, ESCRT proteins have recently been shown to be involved in the formation of the nuclear envelope following mitotic exit3 and an evolutionary role for ESCRT in cellularisation has been proposed4. Disruption of ESCRT function brings about multiple failures in cell division - as such analysis of ESCRT function during this process is essential for our knowledge of how cells divide, and for the disease consequences of ESCRT loss, which include neurodegeneration and cancer. This protein complex is likely to be aided by the actin and microtubule cytoskeletons, which provide cellular membranes with a structural support, and guide the inheritance of other cytoplasmic organelles including mitochondria and Golgi. Thus, the student will also explore the differential role and localisation of actin isoforms in ER segregation at division5. This project will require a combination of biochemistry, molecular genetics, advanced cell biology (fixed- and live-cell imaging), correlative light and electron microscopy and computational reconstruction to perform a detailed analysis of ER shaping and inheritance during cell division and will examine defects in this process when ESCRT function, or cytoskeletal regulators, are compromised.

战略研究优先事项：世界级的生物科学抽象部门需要精确分离整套细胞结构。尽管如此，对真核细胞分裂的研究往往集中在染色体分离上，而对ER在分裂时的分离方式几乎一无所知。该项目的目的是使用先进的成像技术和生物物理技术来补救这一点，以了解内质网如何在有丝分裂和分裂期间正确形成和分布在子细胞之间。内质网（ER）是一个与核膜相连的内膜网络，它贯穿所有真核细胞的细胞质。尽管它的重要性，机制控制适当的继承这个细胞器在分裂仍然在很大程度上是未知的。在细胞分裂过程中，ER必须被重塑，分配成子细胞，并重新组装成功能性ER和密封的核被膜。这个博士学位的目的将是表征由细胞骨架和最近描述的膜运输机械称为ESCRT，在ER的塑造和遗传，过程中发挥的作用适当的细胞器生物合成必不可少。 ESCRT是这种分析的理想靶标，因为它在胞质分裂和内体分选中起重要作用2。此外，ESCRT蛋白最近被证明参与有丝分裂退出后核膜的形成3，并提出了ESCRT在细胞化中的进化作用4。ESCRT功能的破坏会导致细胞分裂的多次失败-因此，在此过程中ESCRT功能的分析对于我们了解细胞如何分裂以及ESCRT丢失的疾病后果（包括神经变性和癌症）至关重要。这种蛋白质复合物可能得到肌动蛋白和微管细胞骨架的帮助，它们为细胞膜提供结构支持，并指导其他细胞质细胞器（包括线粒体和高尔基体）的遗传。因此，学生也将探讨肌动蛋白异构体在内质网分离中的差异作用和定位。该项目将需要生物化学，分子遗传学，先进的细胞生物学（固定和活细胞成像），相关的光学和电子显微镜和计算重建的组合，以执行细胞分裂过程中的ER成形和遗传的详细分析，并将检查ESCRT功能或细胞骨架调节剂时，在这个过程中的缺陷，受到损害。