Connecting Ca2+ and cell migration to development and cancer

将 Ca2 和细胞迁移与发育和癌症联系起来

• 批准号: 1755866
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1755866
• 关键词: Connecting; Ca2+; cell; migration; development

Changes in the concentration of cytosolic Ca2+ drive a multitude of cellular events from those at the very start of life (fertilization), through development and ultimately to those culminating in cell death. These Ca2+ signals often initiate from intracellular Ca2+ stores which includes a variety of acidic organelles such as lysosomes referred to as "acidic Ca2+ stores". Defective signalling through acidic Ca2+ stores has been implicated in a number of disorders including Parkinson disease highlighting the need to understand organellar Ca2+ transport and the cellular processes that it regulates.The neural crest is a transient, migratory population of cells found in all vertebrate embryos that differentiate into a wide range of cell types, including neurons and glial cells of the peripheral nervous system and cartilaginous and skeletal elements in the head. Understanding the mechanisms driving migration is critically important to understand not only morphogenesis but also cancer metastasis - a process to which neural crest migration is often likened.This project builds on our very recent findings that have identified novel Ca2+ transporters on acidic Ca2+ stores and shown that they regulate migration of neural crest cells in vivo. The overall aim is to combine expertise in endo-lysosomal Ca2+ signalling (Patel) and cell migration (Mayor) to further test the hypothesis that acidic Ca2+ stores are required for cell motility. The student will use both chemical and molecular methods to manipulate Ca2+ signaling proteins and examine the effect on cytosolic Ca2+ and migration. This will be achieved using a range of molecular cell biology and imaging approaches, amphibian neural crest cells to study cell migration in vivo, and neuroblastoma, one of the most common childhood cancers, for in vitro analyses.The successful outcome of this project will provide urgently needed molecular insight in to the mechanisms of endo-lysosomal Ca2+ signalling and cell migration during (patho)physiologically relevant processes.

胞质Ca 2+浓度的变化驱动了许多细胞事件，从生命开始（受精），通过发育，最终达到细胞死亡的高潮。这些Ca 2+信号通常起始于细胞内Ca 2+库，其包括各种酸性细胞器，例如称为“酸性Ca 2+库”的溶酶体。通过酸性Ca 2+储存的缺陷信号传导与包括帕金森病在内的许多疾病有关，这突出了理解细胞器Ca 2+转运及其调节的细胞过程的必要性。神经嵴是在所有脊椎动物胚胎中发现的短暂的迁移细胞群，其分化成广泛的细胞类型，包括周围神经系统的神经元和神经胶质细胞以及头部的软骨和骨骼成分。了解驱动迁移的机制不仅对了解形态发生而且对了解癌症转移至关重要-这是一个神经嵴迁移经常被比作的过程。该项目建立在我们最近的发现基础上，这些发现已经确定了酸性Ca 2+商店的新型Ca 2+转运蛋白，并表明它们调节体内神经嵴细胞的迁移。总体目标是结合联合收割机内溶酶体Ca 2+信号传导（Patel）和细胞迁移（Mayor）的专业知识，以进一步检验酸性Ca 2+储存是细胞运动所需的假设。学生将使用化学和分子方法来操纵Ca 2+信号蛋白，并检查对胞质Ca 2+和迁移的影响。这将通过使用一系列的分子细胞生物学和成像方法，两栖动物神经嵴细胞研究细胞迁移在体内，和神经母细胞瘤，最常见的儿童癌症之一，在体外analysis.The成功的结果，该项目将提供迫切需要的分子洞察力内溶酶体钙离子信号和细胞迁移的机制在（病理）生理相关的过程。