Work was conducted via 4 research objectives (RO). RO1 aimed to assess the contribution of lysosomes acidification capacity and localization to induce the formation of the toroidal nucleus. The characterization of the role of lysosomes in mitosis was elaborated in RO2. The identification of lysosomal substrates in mitosis by proteomic analysis was developed in RO3. Finally, the objective of RO4 was to determine the relevance of the formation of toroidal nuclei in cell fate and its importance on malignant transformation.
I completed my project successfully, even under the extraordinary situation experienced in COVID-19 pandemic. The results demonstrated that lysosomes and autophagic vesicles are present and active during cell division and that lysosome acidification capacity and trafficking are important to maintain correct mitotic progression. We demonstrated that impairment of lysosomes induced mitotic errors, which correlated with an increase of the formation of the toroidal nucleus. These findings led us to propose to use the toroidal nucleus as a novel biomarker for chromosomal instability. Although lysosome disruption clearly induced the formation of toroidal nuclei, we corroborated that defects in chromosome segregation is the leading cause for the formation of the toroidal nuclei. We further investigated the presence of autophagic vesicles during mitotic progression and found that functional autophagy is involved in the maintenance of mitosis fidelity. We identified more than 150 novel lysosome substrates specifically during mitosis by proteomic analysis. We further investigated two proteins associated with the cohesin complex that are directly involved in chromosomal segregation. I am last and corresponding author of the peer-reviewed article in one of the top journals in the field (published in 2020, IF: 10.79). Even affected by COVID-19 pandemic, I presented our findings in 6 renowned scientific conferences during the duration of my MSCA Individual Fellowship. My participation to international conferences increased my professional network and I established a fruitful collaboration with Dr Charles Day (Hormel Institute-Mayo Clinic, USA). Following the publication of our manuscript, I was invited as guest editor by two journals “Cells” and “Frontiers in Cell and Developmental Biology” to spearhead the development of special issues on the topic (for 2021). With the support of my MSCA and of companies specialized in science communication, I created 2 videos to broadcast my research project and to highlight our findings (one was launched in 2019 and has more than 1000 views on YouTube, the other was uploaded recently and already reached more than 100 views). I developed educational material to discuss cell biology in primary schools as a Marie Skłodowska-Curie ambassador (only in 2019 due to COVID-19 pandemic). To fulfil my interest in developing my own research laboratory, I participated to internal training at IDIBELL and in February 2020 to a 3-days course focused on laboratory leadership organized by EMBO.
