Roles of cytoplasmic bridges in cell-cell cohesion and communication

Descrizione del progetto

Uno sguardo più attento alle connessioni cellulari

Durante lo sviluppo, le cellule si dividono per produrre altre cellule. Questo processo di solito termina con l’abscissione, ovvero la separazione completa di due cellule appena nate. Tuttavia alcune cellule rimangono collegate attraverso strutture chiamate ponti citoplasmatici. Questi ponti possono svolgere un ruolo importante nel mantenimento della funzione cellulare ma i loro effetti non sono ben compresi. In questo contesto, il progetto CYTO-BRIDGES, finanziato dal CER, studia questi ponti citoplasmatici quali organelli conservati e cruciali per il funzionamento della cellula. I ricercatori esploreranno come questi ponti fungano da collegamenti meccanici e canali di comunicazione tra le cellule collegate. Utilizzando immagini dal vivo e tecniche genetiche avanzate, il progetto studierà la semplice choanoflagellata Salpingoeca rosetta e le complesse cellule staminali embrionali di topo. I risultati miglioreranno la nostra comprensione di come queste strutture influenzino le interazioni cellulari negli organismi multicellulari.

Obiettivo

During development, cells divide and make fate decisions. Canonically, cell division ends with the severing of the link between daughter cells in the process called abscission. Yet, across the tree of life, cells can remain connected through cytoplasmic bridges by delaying or inhibiting abscission. Curiously, while bridges are important conserved structures sustaining cellular function, there are little evidence to explain how bridge impact cell function. The aim of the proposal is to investigate the hypothesis that bridges are conserved organelles critical for cell function by providing unique mechanical connexion and an important inter-cellular communication channel. In particular, we will leverage our expertise in live imaging of cell division and biophysics as well as a combination of newly developed genetic and optogenetic manipulations to determine:
1) The role of bridges as a mechanical coupling between connected cells. We will test the contribution of cytoplasmic bridges in creating a physical link between cells and the consequences of disturbing this cohesion for cell function.
2) The role of bridges as an exchange route between connected cells. We will investigate how the regulated exchange of cellular material through bridges impacts cell function.
As bridges can have a simple or a complex structure that could be critical for their function, we will use 2 model systems: the choanoflagellate Salpingoeca rosetta where a structurally simple bridge sustains cell-cell cohesion, and mouse embryonic stem cells where bridges are structurally more complex. While traditional models of bridges are difficult to manipulate, both our models are easy to culture and provide an experimentally tractable system that can shuttle from a unicellular to a multicellular organisation. The comparison between these two model systems will allow us to understand how a fundamental step of cell division could crucially impact the function of cells in a multicellular context.