Molecular and functional characterization of the spindle matrix in drosophila

果蝇纺锤体基质的分子和功能表征

• 批准号: 402217-2011
• 负责人: Archambault, Vincent
• 金额: $ 2.55万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629145
• 关键词: Molecular; functional; characterization; spindle; matrix

Every living organism must be able to reproduce its cells in order to develop, survive and reproduce. Cell division involves complex molecular mechanisms to ensure the proper partitioning of the cellular content into the newborn cells, and the regulation of the timing and progression of the process. My laboratory uses the fruitfly Drosophila melanogaster as a model organism to answer these questions. Faithful segregation of chromosomes is especially important to the genetic integrity of the cells. The mitotic spindle is a crucial intracellular structure on which chromosomes assemble and migrate during cell division. Initially, the spindle was thought to be made merely of a scaffold of microtubules (tubular proteins) and a few accessory proteins bound to it. More recently, several lines of evidence have indicated that the microtubule-based mitotic spindle relies on an additional structure, the spindle matrix, that surrounds it to give it mechanical support and assists it in its functions. Although we now know the existence of the spindle matrix, we know very little of its molecular composition, its precise functions and how it is regulated. The spindle matrix appears to be derived from the nuclear envelope which surrounds chromosomes before mitosis, but the transformations involved are unknown. This proposal will address these open questions, first by identifying the proteins that are part of the spindle matrix. The functions of these proteins and of their interactions with each other will then be tested by removing them or mutating them, and examining the consequences on the integrity of the spindle matrix and on cell division. This project provides a great opportunity to train graduate students for research in the biological sciences, including cell biology, genetics, molecular biology, biochemistry and microscopy. In the long-term, the technology that we are developing will be used in tackle other crucial and misunderstood aspects of cell cycle regulation and cell division in the context of the fruitfly as an ideal model organism for this type of research.

每个活着的有机体都必须能够繁殖它的细胞，才能发育、生存和繁殖。细胞分裂涉及复杂的分子机制，以确保细胞内容正确地划分到新生细胞中，并调节这一过程的时间和进程。我的实验室用果蝇黑腹果蝇作为模式生物来回答这些问题。染色体的忠实分离对细胞的遗传完整性尤其重要。有丝分裂纺锤体是细胞内的重要结构，染色体在细胞分裂过程中在其上组装和迁移。最初，纺锤体被认为只是由微管(管状蛋白)和少数附属蛋白结合而成的支架。最近，有几条证据表明，基于微管的有丝分裂纺锤体依赖于一个额外的结构，即纺锤体基质，它包围着它，给予它机械支持，并帮助它发挥功能。虽然我们现在知道纺锤体基质的存在，但我们对它的分子组成、确切的功能以及它是如何调节的知之甚少。纺锤体基质似乎来自有丝分裂前包裹在染色体周围的核膜，但涉及的转化尚不清楚。这项提议将首先通过识别属于纺锤体基质的蛋白质来解决这些悬而未决的问题。然后，将通过移除或突变这些蛋白质以及它们之间的相互作用来测试它们的功能，并检查它们对纺锤体基质完整性和细胞分裂的影响。这个项目提供了一个很好的机会培养研究生从事生物科学的研究，包括细胞生物学、遗传学、分子生物学、生物化学和显微镜。从长远来看，我们正在开发的技术将被用于解决细胞周期调节和细胞分裂的其他关键和被误解的方面，作为这类研究的理想模式生物。