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

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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.