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Janeth Catalina Manjarrez González

PhD student

Email: j.c.manjarrez-gonzalez@qmul.ac.uk

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Project title: A molecular study of mechanisms that drive aneuploidy in cancers

Summary: Aneuploidy and multinucleation are two key hallmarks of most aggressive cancers, and they could arise from errors in the process of chromosome segregation. To ensure the accurate segregation of chromosomes, chromosomes must be properly attached to microtubules during mitosis and meiosis. Chromosome-microtubule attachment is mediated by a multiprotein macromolecular structure, the Kinetochore. Human kinetochores are composed of more than 100 distinct proteins. Among them are two large evolutionarily conserved protein networks: constitutive centromere-associated network (CCAN) and KMN network. The networks ensure proper kinetochore assembly and kinetochore-microtubule interaction, and subsequently the accurate segregation of chromosomes. My project aims to explore how human cells tolerate normally occurring loss of function genomic variants in CCAN and KMN network proteins and their interactors. Using bioinformatic tools, I will identify loss of function variants in CENP-C and SKA complex interactors in gnomAD and cancer databases. Using cell biology methods, I will investigate the extent to which the variants can promote chromosome missegregation and multinucleation associated DNA Damage (MADD). The research is expected to provide insight into the molecular cause and cellular impact of multinucleation and aneuploidy observed in cancer tissues.

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