Thesis Project Description:
Cell division is a fundamental biological process that is essential for multiple aspects of animal physiology, including cell proliferation and differentiation, tissue growth and repair. Its dysfunction leads to several human pathologies, including tumour development and tissue degeneration. Cell division involves strong cell shape changes and thus heavily relies on the redistribution and cooperation of force-generating cytoskeletal filamentous proteins, notably actin filaments and microtubules. While the requirement of actin and microtubules for successful cell division is not questioned, their precise organization and interaction with other proteins is still poorly understood. In particular, little is known about the functional contribution of septins, a family of proteins which was recently recognized as a novel component of the animal cytoskeleton. Septins are essential for the successful completion of cell division and form protomers which can polymerize into filaments that associate with actin and microtubules. My project aims at developing optical and biological tools to decipher the organization of septins and their interaction with actin and microtubules during cell division. The topic addressed is highly interdisciplinary in co-supervision between I. Fresnel and Centre de Recherche en Cancérologie de Marseille (CRCM). Key open questions will be addressed to identify the molecular determinants that localize septins to cytoskeletal subsystems. Dedicated optical imaging methods will be implemented in collaboration with HORIBA, with the goal to measure filament organization at high spatial resolution and potentially in real time. These measurements will be implemented using polarized fluorescence imaging on two systems: in vitro reconstituted cytoskeletal filaments from purified components, in collaboration with the international partner (AMOLF, The Netherlands), and dividing mammalian cells, with the co-supervisor at CRCM. The molecular mechanisms at the origin of inter-filament organization will be investigated using septin mutants impaired for polymerization or with modified selectivity for actin or microtubules.
Interdisciplinary Research Axis:
Master in Physics
Università degli Studi di Milano, Italy