Mechanisms governing the formation and correction of erroneous kinetochore-microtubule attachments

错误着丝粒-微管附着的形成和纠正机制

基本信息

批准号：
2596911
负责人：
金额：
--
依托单位：
University of Warwick
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2596911
关键词：
Mechanisms governing formation correction erroneous

项目摘要

Cell division is an essential but risky business. Duplicated chromosomes are segregated between the two new cells with the aid of the spindle, a bipolar guidance scaffold, which is connected to each chromosome through the kinetochore. Kinetochores are self-correcting molecular machines that generate forces to move chromosomes. They are also able to identify and eliminate incorrect kinetochore-spindle attachments. This is key as persistence of incorrect attachments can lead to new cells gaining or losing entire chromosomes, known as aneuploidy, which is associated with reproductive failure, ageing, and cancer. In this project the student will investigate the life cycle of incorrect attachments with a focus on syntelics; in this situation the kinetochores on a duplicated chromosome pair are attached to the same spindle pole (rather than opposite poles). They will track kinetochore conformation, attachment, and phosphorylation status, and create a model of events from creation to resolution of these incorrect attachments. To achieve this, the student will utilise and gain extensive experience in: Advanced fluorescent microscopy techniques, including fixed cell spinning disk confocal microscopy and live cell lattice light sheet microscopy Development and use of computational modelling and analysis pipelines Essential molecular biology techniquesWe expect this combination of cell and computational biology to provide new insights into how human cells ensure they maintain the correct number of chromosomes.

细胞部门是必不可少但冒险的业务。重复的染色体借助纺锤体（双极引导支架）在两个新细胞之间隔离，该染色体通过动力学连接到每个染色体。动力学是产生动力移动染色体的自我校正的分子机器。他们还能够识别和消除不正确的动力学主轴附件。这是关键，因为不正确的附着的持久性会导致新细胞获得或失去整个染色体，称为非整倍性，这与生殖衰竭，衰老和癌症有关。在这个项目中，学生将研究不正确依恋的生命周期，重点是syntelics；在这种情况下，重复的染色体对上的动力学与同一主轴杆连接（而不是相对的杆）。他们将跟踪动力学构象，附件和磷酸化状态，并创建从创建到解决这些不正确附件的事件模型。为此，学生将利用并获得丰富的经验：高级荧光显微镜技术，包括固定细胞旋转盘共聚焦显微镜和活细胞晶格光片显微镜显微镜的开发以及计算建模和分析管道的使用必不可少的分子生物学技术，我们期望细胞和计算生物学的这种结合，以确保将人类的细胞保持在正确的洞察力中，以确保将人类保持在正确的小组中。