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Interplay between the exocyst complex and Tor signal transduction in the fission yeast Schizosaccharomyces pombe

裂殖酵母裂殖酵母中外囊复合体与 Tor 信号转导之间的相互作用

基本信息

批准号：
1622215
负责人：
金额：
--
依托单位：
UNIVERSITY OF EXETER
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-1622215
关键词：
Interplay between exocyst complex Tor

项目摘要

Regulation to ensure correct growth and development is paramount for the survival of every organism. For cellular homeostasis to be maintained, cells have evolved with ever more complex processes that regulate growth and division. All these processes involve the sensing of the environment for nutrients or stressors. Stressors affect specific proteins in the plasma membrane which act as molecular switches to turn on stress signalling pathways to reduce growth of the organism. Conversely, nutrient rich environments promote growth through the nutrients themselves activating signalling networks that promote cellular growth.Once activated, these signalling networks control cellular processes involved in modulating cell growth and size. One of these includes intracellular trafficking. Both exocytosis and endocytosis play key roles in the delivery of materials needed to protrude the cell periphery, but also the removal nutrient transporters, receptors, and lipid domains in the plasma membrane so that growth occurs in the correct cellular location and at a regulated rate. One trafficking complex that has been implicated in both exo- and endocytosis is the exocyst complex.The exocyst is a conserved hetero-octameric complex that is thought to tether cargoes to the plasma membrane. While most of these exocyst related cargoes are still awaiting identification, proteins involved in nutrient uptake have been shown to be dependent on exocyst mediated exocytosis. Mutation of exocyst members also results in defects in endocytosis, revealing a role for this complex in the retrograde transport of these components too. Furthermore members of the exocyst have been implicated in the activation of stress signalling pathways. This places the exocyst as a potential master regulator of stress and nutrient sensing via its modulation of the level of stress and nutrient sensors at the cell surface and possible bridging of this to signalling networks.A PhD student will test the hypothesis that the exocyst complex is involved in nutrient sensing through regulation of Tor signalling. They will tackle this question using a combination of genetics, cell biology and biochemical techniques, and by exploiting the experimental power of the fission yeast S. pombe.The PhD student will tackle this question by exploiting the experimental power of the fission yeast S. pombe in conjunction with vertebrate neuronal cultures. Using a range of genetic, biochemical and fluorescent imaging techniques the PhD student will use yeast to identify the partners of the exocytic system in actin organisation and apply the conclusions to vertebrate neurons. Due to their inherent complexity, variations in neuron morphology are currently practically impossible to assess. An automated image processing framework will be developed to objectively extract morphological information from fluorescent images of the cells' borders, from which quantitative conclusions may be drawn. This tool will help probe features of cell shape across classes of organism. All in all, these data will provide novel insights into a universal mechanism that is utilised throughout evolution, in fungi, plants and animals.

确保正确生长和发育的监管对每个有机体的生存都是至关重要的。为了维持细胞的动态平衡，细胞已经进化出更复杂的过程来调节生长和分裂。所有这些过程都涉及到感知环境中的营养物质或压力源。应激源影响质膜中的特定蛋白质，这些蛋白质充当分子开关，开启胁迫信号通路，减少有机体的生长。相反，营养丰富的环境通过营养本身激活促进细胞生长的信号网络来促进生长。一旦激活，这些信号网络就控制着参与调节细胞生长和大小的细胞过程。其中之一包括细胞内贩运。胞吐作用和内吞作用都在运送突起细胞外围所需的物质方面发挥着关键作用，但也在清除质膜中的营养转运体、受体和脂类结构域以使生长在正确的细胞位置和调节的速度中发挥关键作用。胞外和胞内转运的复合体之一是胞外复合体。胞外复合体是一种保守的异八聚体复合体，被认为可以将货物拴在质膜上。虽然大多数这些与胞囊有关的货物仍在等待鉴定，但参与营养吸收的蛋白质已被证明依赖于胞囊介导的胞吐作用。胞外囊成员的突变也会导致内吞作用的缺陷，这也揭示了这种复合体在这些成分的逆行运输中的作用。此外，外囊的成员还参与了胁迫信号通路的激活。这使胞囊通过调节细胞表面的压力和营养传感器的水平，并可能将其连接到信号网络，成为潜在的压力和营养感知的主调节器。一名博士生将通过调节Tor信号来检验这一假设，即胞囊复合体参与营养感知。他们将使用遗传学、细胞生物学和生化技术的组合来解决这个问题，并通过利用分裂酵母S.pombe的实验能力来解决这个问题。博士生将通过利用分裂酵母S.pombe的实验能力与脊椎动物神经元培养相结合来解决这个问题。利用一系列遗传、生化和荧光成像技术，这位博士生将使用酵母来识别肌动蛋白组织中胞外系统的伙伴，并将结论应用于脊椎动物神经元。由于其固有的复杂性，神经元形态的变异目前几乎不可能评估。将开发一个自动图像处理框架，从细胞边界的荧光图像中客观地提取形态信息，从中可以得出定量的结论。这个工具将有助于探测不同类别生物体的细胞形状特征。总而言之，这些数据将为在真菌、植物和动物的整个进化过程中使用的普遍机制提供新的见解。