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Roles of cytoplasmic bridges in cell-cell cohesion and communication

Project description

A closer look at cell connections

During development, cells divide to produce more cells. This usually ends in abscission, the process by which two new born cells separate completely. However, some cells remain connected through structures called cytoplasmic bridges. These bridges can play an important role in maintaining cellular function, but their effects are not well understood. In this context, the ERC-funded project CYTO-BRIDGES investigates these cytoplasmic bridges as conserved organelles crucial for cell function. Researchers will explore how these bridges serve as mechanical links and communication channels between connected cells. Using live imaging and advanced genetic techniques, the project will study the simple choanoflagellate Salpingoeca rosetta and complex mouse embryonic stem cells. The findings will enhance our understanding of how these structures influence cellular interactions in multicellular organisms.

Objective

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.

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(opens in new window) ERC-2024-STG

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Host institution

UNIVERSITEIT UTRECHT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 500 000,00
Address
HEIDELBERGLAAN 8
3584 CS Utrecht
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

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€ 1 500 000,00

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