Understanding the inheritance of the Endoplasmic Reticulum during cell division

战略研究重点：世界一流的生物科学摘要分裂需要精确分离整个细胞结构集。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。本项目的目的是利用先进的成像技术和生物物理技术来弥补这一点，以了解内质网在有丝分裂和分裂过程中如何在子细胞之间正确形成和分布。内质网（ER）是一个与核膜相连的内膜网络，并延伸到所有真核细胞的细胞质中。尽管它很重要，但在分裂时控制这种细胞器适当遗传的机制仍然很大程度上是未知的。在细胞分裂过程中，内质网必须被重塑，分裂成子细胞，并重新组装成功能性内质网和密封的核膜。本博士的目的是描述细胞骨架和最近描述的称为ESCRT的膜运输机制在内质网形成和遗传中的作用，这是正常细胞器生物发生所必需的过程。ESCRT在细胞质分裂和内体分选中起着重要作用，因此是该分析的理想靶点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，并提出了ESCRT在细胞化中的进化作用。ESCRT功能的破坏会导致细胞分裂的多重失败，因此，对这一过程中ESCRT功能的分析对于我们了解细胞如何分裂以及ESCRT缺失导致的疾病后果（包括神经变性和癌症）至关重要。这种蛋白复合物可能得到肌动蛋白和微管细胞骨架的辅助，它们为细胞膜提供结构支持，并指导包括线粒体和高尔基体在内的其他细胞器的遗传。因此，学生还将探索肌动蛋白同工型在分裂5的内质网分离中的不同作用和定位。该项目将需要结合生物化学、分子遗传学、高级细胞生物学（固定细胞和活细胞成像）、相关光学和电子显微镜以及计算重建来详细分析细胞分裂过程中内质网的形成和遗传，并检查当ESCRT功能或细胞骨架调节因子受到损害时这一过程中的缺陷。

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.