Molecular and functional characterization of the spindle matrix in drosophila

每一个活的有机体都必须能够繁殖它的细胞，以发展，生存和繁殖。细胞分裂涉及复杂的分子机制，以确保细胞内容物正确分配到新生细胞中，并调节该过程的时间和进展。我的实验室使用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特别重要。有丝分裂纺锤体是细胞分裂过程中染色体聚集和迁移的重要细胞内结构。最初，纺锤体被认为仅仅是由微管（管状蛋白）和一些与其结合的辅助蛋白组成的支架。最近，一些证据表明，以微管为基础的有丝分裂纺锤体依赖于一个额外的结构，即纺锤体基质，它围绕着它，给它以机械支持，并帮助它发挥功能。虽然我们现在知道纺锤体基质的存在，但我们对其分子组成，其精确功能以及如何调节知之甚少。纺锤体基质似乎来源于有丝分裂前包围染色体的核膜，但涉及的转化尚不清楚。这项提案将解决这些悬而未决的问题，首先通过识别蛋白质的纺锤体矩阵的一部分。这些蛋白质的功能及其相互作用将通过去除或突变它们来测试，并检查对纺锤体基质完整性和细胞分裂的影响。该项目提供了一个很好的机会，培养研究生在生物科学的研究，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用于解决细胞周期调控和细胞分裂的其他关键和误解方面，而果蝇是这类研究的理想模式生物。

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.