Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Molecular mechanisms regulating the kinetochore-microtubule interaction in mitosis.

Funder Wellcome Charity-funded
Recipient organisation University of Dundee
Funding £3.8M
Period Apr 2012 — Sept 2019

In plain English

AI plain-English summary

Every time a human cell divides, it must pull its duplicated chromosomes apart into two identical sets—and when that process goes wrong, the result can be cancer or a condition like Down syndrome. The machinery that performs this separation is a microscopic tug-of-war: protein structures called kinetochores attach to rope-like microtubules that yank the chromosomes to opposite ends of the cell. This project aims to discover exactly how cells regulate that attachment, ensuring it is strong enough to work but flexible enough to release when the time is right. The researchers are studying budding yeast because its genetics are easy to manipulate and its protein details are well mapped, and because the core mechanisms are the same in human cells. This is fundamental science—there is no immediate medical application. But understanding the molecular rules of chromosome segregation could eventually reveal why some cells become aneuploid (with too many or too few chromosomes) and point toward new ways to detect or treat the diseases that result from that instability.

View original technical description
To maintain their genetic integrity, eukaryotic cells must segregate their chromosomes properly to opposite poles during mitosis. The unravelling of the mechanisms that ensure high-fidelity chromosome segregation should improve our understanding of various human diseases such as cancers and congenital disorders (e.g. Down syndrome), which are characterized by chromosome instability and aneuploidy. Sister chromatid segregation during mitosis mainly depends on the forces generated by microtubules that attach to kinetochores. For proper chromosome segregation, kinetochores must interact with spindle microtubules efficiently and this interaction must develop correctly to achieve proper chromosome segregation in the subsequent anaphase. Our research goal is to discover and characterize the molecular mechanisms by which cells regulate these vital processes of kinetochore-microtubule interactions. We investigate the kinetochore-microtubule interactions in budding yeast because of the amenable genetics and detailed proteomic information in this organism. The basic principles of kinetochore-microtubule interactions are similar in yeast and vertebrate cells. Because of this conservation of basic mechanisms, it is likely that results from the yeast system will be of direct relevance to chromosome segregation mechanisms in human cells.

View the original record at the funder ↗

Researchers

Tomoyuki Tanaka (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Molecular mechanisms of kinetochore-microtubule interaction
Kinetochore–microtubule interactions: steps towards bi-orientation
Mechanisms orienting chromosomes in mitosis and meiosis.
Mechanisms for efficient kinetochore capture by spindle microtubules
Mechanisms ensuring sister kinetochore bi-orientation on the mitotic spindle

Original classification

Principal Research Fellowship (New)

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.