Roles of cytoplasmic bridges in cell-cell cohesion and communication

Descripción del proyecto

Un análisis más detallado de las conexiones entre células

A lo largo del desarrollo, las células se dividen para producir más células. Ello suele acabar en abscisión, el proceso por el que dos células recién nacidas se separan por completo. Sin embargo, algunas células permanecen conectadas a través de estructuras denominadas «puentes citoplasmáticos». Dichos puentes pueden desempeñar un papel importante en el mantenimiento de la función celular, pero sus efectos no se conocen bien. En este contexto, el proyecto CYTO-BRIDGES, financiado por el Consejo Europeo de Investigación, investiga los puentes citoplasmáticos como orgánulos conservados cruciales para la función celular. Los investigadores estudiarán cómo los puentes sirven de enlaces mecánicos y canales de comunicación entre células conectadas. Mediante imágenes en directo y técnicas genéticas avanzadas, el proyecto estudiará el sencillo coanoflagelados «Salpingoeca rosetta» y las complejas células madre embrionarias de ratón. Los hallazgos mejorarán nuestra comprensión sobre cómo influyen estas estructuras en las interacciones celulares de los organismos pluricelulares.

Objetivo

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.