Investigating Kinetochore Plasticity during Mitosis

About the Project

PROJECT DESCRIPTION: Aberrant cell division (mitosis) is a hallmark of cancer and is present in more than 90% of solid tumours and 50% of blood cancers. During cell division structures such as centrosomes, the mitotic spindle, and kinetochores collaborate to ensure that each copy of the duplicated chromosomes is properly segregated to the newly formed daughter cells. The kinetochore is a large, protein-rich structure that assembles onto chromosomes only during mitosis. The kinetochore has two major functions during mitosis; first it acts as a major signalling hub, and secondly it forms the site of interaction between microtubules of the mitotic spindle and the dividing chromosomes, in this manner playing a dual role in ensure genome fidelity. Recent studies have shown that the kinetochore is more complex and dynamic than previously thought. The proposed project will use state-of-the-art proteomics approaches to explore the composition and interaction network of the kinetochore under different states of microtubule attachment. This work will provide critical insights into how mitotic signalling and structures can be altered in cancer and may reveal new therapeutic targets to improve patient outcomes.

LOCATION: The CHU de Québec–Université Laval is one of the largest French-language medical research centers in North America. It is also the only center in Quebec whose work spans the entire continuum of life sciences, from basic research to clinical and translational studies. Thanks to the excellence of its research teams and its state-of-the-art facilities, the organization has built a strong national and international reputation and stands out for its outstanding achievements.

Professor Sabine Elowe’s laboratory is located in a brand-new research center inaugurated in 2025 in Quebec City. This center is a strategic pillar for the future of health research, focusing on cutting-edge fields and offering privileged access to advanced technological equipment, fostering innovation and interdisciplinary collaboration. https://www.crchudequebec.ulaval.ca/en/researcher/sabine-elowe/

See also the lab website @ https://www.elowelab.ca/

Funding Notes

Fully-funded project.

References

Selected lab references:
1. ARHGEF17/TEM4 regulates the cell cycle through control of G1 progression.
Prifti DK, Lauzier A, Garand C, Calvo E, Devillers R, Roy S, Dos Santos A, Descombes L, Trudel B, Laplante M, Bordeleau F, Elowe S.
J Cell Biol. 2025 Mar 3;224(3):e202311194. doi: 10.1083/jcb.202311194. Epub 2025 Feb 4.
2. Recent insights into the causes and consequences of chromosome mis-segregation.
Devillers R, Dos Santos A, Destombes Q, Laplante M, Elowe S.
Oncogene. 2024 Oct;43(43):3139-3150. doi: 10.1038/s41388-024-03163-5. Epub 2024 Sep 15.
3. Considerations for studying phosphorylation of the mitotic checkpoint pseudokinase BUBR1.
Gama Braga L, Garand C, Elowe S.
Methods Enzymol. 2022;667:507-534. doi: 10.1016/bs.mie.2022.03.045. Epub 2022 Apr 13.
PMID: 35525552 In LibraryView PDF
4. BUBR1 Pseudokinase Domain Promotes Kinetochore PP2A-B56 Recruitment, Spindle Checkpoint Silencing, and Chromosome Alignment.
Gama Braga L, Cisneros AF, Mathieu MM, Clerc M, Garcia P, Lottin B, Garand C, Thebault P, Landry CR, Elowe S.