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）已在许多人类肿瘤中观察到，但其机制是通过 哪些细胞变成非整倍体还不知道。 主轴功能缺陷 是一种可能的机制。 的广泛目标 这项计划中概述的研究是为了确定在基因治疗过程中重要的基因。 利用酵母遗传学、分子生物学、 生物化学、体内和体外研究，以研究 纺锤体伸长; B.调查这 有丝分裂中步骤应该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新的 抗癌治疗的靶点。 最近在S. 啤酒。 晚期有丝分裂中期ASE 1的定位 后期/末期表明它可能对纺锤体的伸长很重要。 的 申请人的研究将集中于确定微管结合 ASE 1的特性，鉴定后期所需的其他基因， 遗传筛选与ASE 1具有重叠功能的基因，和 开发一种体外系统，其中纺锤体伸长被重建， 最终得到纯化的组分。 最终，类似的人类基因将 并研究它们在恶性转化中的作用。 申请人之前的培训包括严格的基础科学 背景和丰富的临床经验。 这个项目是 选择，因为它允许她联合收割机结合她的兴趣，在微管为基础的 她对肿瘤学的临床兴趣。 此外，她将 获得酵母遗传学和分子生物学的强大技术的专业知识 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.