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Expansion microscopy in zebrafish embryo to study primary cilia function during cardiovascular development and diseases

Project description

Imaging-based approach to study primary cilia function during cardiogenesis

Cilia are microtubule-based hair-like organelles on the surface of almost all cell types. They are involved in fundamental processes such as motility, signalling and mechano-sensing, which explains why cilia-related disorders (ciliopathies) affect many organ systems. Cardiovascular defects are common in patients with ciliopathies, and ciliary protein mutations in patients with congenital heart diseases suggest cilia’s important role in cardiogenesis. The EU-funded ZEBREXPANSION project aims to understand the function of primary cilia in cardiovascular development and diseases. The objective is to apply an innovative imaging-based approach in human ciliated cells and zebrafish models to investigate cilia assembly, maintenance and disassembly, and their correlation with essential regulatory functions during cardiogenesis.

Objective

This project aims at revealing the function of primary cilia during cardiovascular development and cardiovascular diseases, with a specific focus on cardiac valves, through an imaging approach based on expansion light microscopy. Cilia are evolutionary conserved organelles, involved in fundamental processes such as motility, signalling and mechano-sensing, associated with a group of developmental diseases termed ciliopathies. Cardiovascular defects are common in patients diagnosed with ciliopathies and genetic studies have identified mutations in genes coding for ciliary proteins in patient suffering from congenital heart diseases, suggesting an important role for this organelle in cardiogenesis. In particular, it has been shown that DZIP1, a cilia related protein involved in ciliogenesis, is mutated in patients. However, little is known about molecular mechanisms underlying DZIP1 abnormal function at developmental stages of valvulopathies. Using an innovative imaging-based approach in human ciliated cells and in zebrafish, we will investigate if cilia assembly, maintenance and disassembly are correlated with essential regulatory functions of DZIP1 during cardiogenesis, more precisely in endocardial cells (EdCs) during valvulogenesis. We will test if the protein DZIP1/Iguana function is not restricted to ciliogenesis in differentiated cells, but displays dynamic functions at centrioles and in the cytoplasm, that are important for tissue-remodelling. My multidisciplinary approach will allow me to tackle this question from the molecular and structural to the cellular and tissue-scale.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
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.

€ 212 933,76
Address
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ London
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 933,76
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