Mécanismes moléculaires de la division cellulaire

 

Gilles Hickson

Centre de recherche du CHU Ste-Justine

 

Domaine : cancer

Programme chercheurs-boursiers - Junior 2

Concours 2014-2015

The global aim of my research program is to understand the molecular mechanisms of cell division, in particular the final phase, cytokinesis, which physically partitions one cell into two. The goal is two-fold, encompassing advances in basic science while working to identify potential targets for anti-cancer therapies. Errors in the timing, placement or execution of cytokinesis lead to genomic abnormalities that can lead to cancer. The cytokinesis machinery must be extremely robust to ensure that the staggering numbers of cell divisions throughout our lifetimes are successful. Over-engineering of the process ensures fidelity but makes deciphering the molecular mechanisms all the more challenging. Yet a molecular understanding of cytokinesis represents an important goal for both cell biology and medicine.

Cytokinesis occurs in stages. First, a contractile ring (CR) self-assembles beneath the plasma membrane to physically pinch the cell in half. Second, a stable intercellular bridge, comprising the midbody and midbody ring (MR), forms. Finally, the bridge is severed. Cytokinesis is so fundamental to life that evolution has conserved the cellular machinery controlling it.  Although we know the identities of the key components of the machinery, we still have much to understand about how they operate together in space and time to promote the faithful execution of cytokinesis. We utilise the advantages of the fruitfly, Drosophila melanogaster, as a genetically tractable system to dissect cytokinesis, which we observe using high-resolution live-cell microscopy techniques. Specifically, we aim to understand precisely how the CR becomes the MR. We also aim to test how the genes involved in this process behave in human cancer cells. Our work will shed light on the fundamental mechanisms of cell division and serve to identify new potential drug targets against cancer.