SPINDLE DYNAMICS AND CHROMOSOME MOVEMENT DURING ANAPHASE

描述(申请人描述)：染色体数目异常 (非整倍体)在许多人类肿瘤中被观察到，但其机制是通过 目前尚不清楚哪些细胞会变成非整倍体。主轴功能缺陷 后期是一种可能的机制。该计划的总体目标 这项提案中概述的研究是识别在 后期利用酵母遗传学、分子生物学、 生物化学、体内和体外研究以探讨其作用机制 宫颈葡萄球菌B期纺锤体的伸长研究 有丝分裂的步骤应该会产生有用的信息来帮助解释 人类癌症的病理生理学以及潜在地提供了新的 抗癌治疗的靶点。 最近发现了一个后期特异的基因--ase1。 酿酒。ASE-1在晚期有丝分裂中区的定位 后期/末期提示它对纺锤体的伸长可能是重要的。这个 申请者的研究将集中在确定微管结合上 特性，确定后期所需的其他基因。 对与ASE1有重叠功能的基因进行遗传筛选，以及 开发一种体外系统，在该系统中，纺锤体的伸长可以重组， 最终用提纯的成分。最终，类似的人类基因将 并对其在恶性转化中的作用进行了研究。 申请者之前的培训包括严格的基础科学 背景以及丰富的临床经验。这个项目是 之所以被选中，是因为这让她能够将自己对微管的兴趣结合起来 她在肿瘤学方面的临床兴趣的活动。此外，她还将 掌握强大的酵母菌遗传学和分子生物学技术 生物学。这次培训将为她提供一个理想的发展环境 成为一名独立的调查员，长期目标是继续 研究的重点是了解人类癌症的病理生理学。

DESCRIPTION (Applicant's Description): Abnormal chromosome number (aneuploidy) has been observed in many human tumors but the mechanism by which cells become aneuploid is not known. Defective spindle function during anaphase is one possible mechanism. The broad objective of the research outlined in this proposal is to identify genes important during anaphase and use the combination of yeast genetics, molecular biology, biochemistry, in vivo and in vitro studies to investigate the mechanism of spindle elongation in S. cervisiae during anaphase B. Investigating this step in mitosis should yield useful information to help explain aspects of the pathophysiology of human cancers as well as potentially provide new targets for anticancer treatment. One anaphase specific gene, ASE1, has recently been identified in S. cerevisiae. The location of ASE1 at the mitotic midzone in late anaphase/telophase suggests it may be important for spindle elongation. The research of the applicant will focus on determining the microtubule binding properties of ASE1, identifying other genes required for anaphase using a genetic screen for genes that have overlapping function with ASE1, and developing an in vitro system in which spindle elongation is reconstituted, ultimately with purified components. Eventually, analogous human genes will be identified and their role in malignant transformation studied. The applicant's prior training includes both a rigorous basic science background as well as extensive clinical experience. This project was selected because it allows her to combine her interests in microtubule-based activities with her clinical interests in oncology. In addition, she will gain expertise in the powerful techniques of yeast genetics and molecular biology. This training will provide an ideal environment for her to develop into an independent investigator with the long-term goal of continued research focused on understanding the pathophysiology of human cancers.