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Skeletal Muscle-Endothelial Cell Crosstalk in Muscle Plasticity and Disease

Project description

The underlying biology in muscle wasting

Many diseases such as cancer as well as ageing may lead to loss of muscle mass and function, known as muscle wasting. Despite its importance in overall health, there are no effective therapies for muscle wasting, as the underlying biology is poorly understood. While research has focused on intracellular pathways, less is known about how muscle fibers interact with endothelial cells (ECs), which supply blood and nutrients. With the support of the Marie Skłodowska-Curie Actions programme, the SMECC project will investigate muscle EC communication using molecular biology, omics, and advanced imaging tools in innovative mouse models. By clarifying how ECs influence muscle growth and function, researchers hope to identify novel therapeutic strategies to combat muscle wasting.

Objective

The maintenance of skeletal muscle mass and function is critically important in various conditions, including aging, cancer, muscular dystrophies, and more. It presents a considerable societal concern, impacting not only individual health but also imposing substantial healthcare expenditures. Despite its clinical relevance, there are currently no fully effective treatments to prevent or reverse muscle wasting due to an incomplete understanding of the involved mechanisms. While much attention has been given to intracellular signalling regulating muscle size, such as the Akt-mTORC1 pathway, the role of muscle perfusion and paracrine interactions between muscle fibers and endothelial cells (ECs) remains poorly understood. Recent studies point to the strong interconnection between muscle fibers and ECs, highlighting their reciprocal influence on each other's function. This project aims to illuminate these interactions, exploring how changes in muscle mass influence protein homeostasis in ECs and how alterations in ECs' proliferation and permeability impact muscle physiology. To address these questions, we will utilize cutting-edge technologies including molecular biology, animal phenotyping, histology, omics, and advanced bioimaging techniques such as tissue clearing and light sheet fluorescence microscopy, while employing innovative models to elucidate the mechanisms underlying in vivo changes in a cell-type specific manner. We will use novel tissue-specific mouse lines, such as MetRS mice, to monitor protein homeostasis within defined time windows, allowing for the study of muscle-EC crosstalk. The anticipated outcomes of this project include a deeper understanding of how ECs and muscle fibers communicate during changes in muscle size and function. By exploring these interactions, we aim to uncover key molecular mechanisms that govern muscle-EC interplay, enhancing our knowledge of ECs' role in muscle biology and guiding future therapeutic strategies.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITA DEGLI STUDI DI PADOVA
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.

€ 209 483,28
Address
VIA 8 FEBBRAIO 2
35122 PADOVA
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
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Total cost

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