Understanding error correction for chromosome bi-orientation using in vitro reconstitution

了解使用体外重构对染色体双向进行纠错

• 批准号: BB/X014517/1
• 负责人: Tomoyuki Tanaka
• 金额: $ 78.3万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX014517%2F1
• 关键词: Understanding; error; correction; chromosome; bi

Human cells store their genetic information in 46 chromosomes. Therefore, to maintain vital genetic information, a complete set of chromosomes must be inherited precisely by each daughter cell when cell division happens. Errors in this chromosome inheritance cause cell death and various human diseases, such as genetic abnormalities and cancers. Our research goal is to understand the fundamental mechanisms that ensure accurate chromosome inheritance when cells divide. These mechanisms involve an efficient and correct interaction between a chromosome and a cellular apparatus called the mitotic spindle, which drives chromosome motions into the new daughter cells. To examine chromosome interaction with the mitotic spindle in fine detail, we will recreate this process outside of the cell, using defined or purified cellular components. By doing so, we can adjust the density of the chromosome interaction with the mitotic spindle in a microscopy field. This will allow us to observe the details of this interaction and to analyse how errors in this interaction are resolved. To validate that the process recreated outside of the cell is physiologically relevant, we will compare it with the actual process inside the cell. Our research should contribute to our understanding of how various human diseases involving errors in chromosome inheritance arise, and how they might be prevented.

人类细胞将其遗传信息存储在46条染色体中。因此，为了保持重要的遗传信息，当细胞分裂发生时，一套完整的染色体必须精确地由每个子细胞继承。这种染色体遗传的错误导致细胞死亡和各种人类疾病，如遗传异常和癌症。我们的研究目标是了解细胞分裂时确保染色体准确遗传的基本机制。这些机制涉及染色体和称为有丝分裂纺锤体的细胞装置之间的有效和正确的相互作用，纺锤体驱动染色体运动进入新的子细胞。为了更详细地研究染色体与有丝分裂纺锤体的相互作用，我们将使用确定的或纯化的细胞成分在细胞外重现这一过程。通过这样做，我们可以在显微镜视野中调节染色体与有丝分裂纺锤体相互作用的密度。这将使我们能够观察这种相互作用的细节，并分析如何解决这种相互作用中的错误。为了验证在细胞外重新创建的过程与生理相关，我们将其与细胞内的实际过程进行比较。我们的研究应该有助于我们理解各种涉及染色体遗传错误的人类疾病是如何产生的，以及如何预防它们。