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Glycosaminoglycan biosynthesis: deciphering the divergent step

Project description

Decoding the sugar code of human tissue

Glycosaminoglycans, or GAGs, are sugar molecules that constitute a significant part of the extracellular matrix. Since GAGs are involved in everything from cell growth to wound healing, they can cause neurological disease, cardiovascular disease, diabetes, and cancer if they become dysfunctional. For this reason, it is necessary to understand how these complex sugars are constructed in human tissue. Supported by the Marie Skłodowska-Curie Actions programme, the GlycoDIVE project aims to map the molecular equipment for GAG assembly. It will focus on the heparan sulphate and chondroitin/dermatan sulphate biosynthetic enzymes. Integrating biochemistry, structural biology, and cell biology, the project is expected to shed light on the molecular guidelines of GAG assembly and open a path to future therapies.

Objective

Glycosaminoglycans (GAGs) are negatively charged polysaccharides that form a key part of the extracellular matrix in animal tissues, from marine corals to humans. They play crucial roles in cell signaling, mediating processes such as embryonic development, cell growth and proliferation, cell adhesion, anticoagulation, and wound repair. Given their diverse functions, GAG dysregulation is linked to various medical conditions, including neurological, cardiovascular, infectious, and inflammatory diseases, as well as diabetic complications and cancer. While much is known about their roles in health and disease, gaps remain in understanding of how they are synthetized in human tissues. This project aims to investigate glycosyltransferases that participate in the synthesis of heparan sulfate and chondroitin/dermatan sulfate at a molecular level. By integrating biochemistry, structural biology (including cryo-electron microscopy and X-ray crystallography), and cell biology, our goal is to uncover the molecular mechanisms that distinguish these polysaccharides. Thus, this project aims to address fundamental questions in GAG biosynthesis and to provide a molecular basis for the development of GAG-based therapies in future studies.

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Programme(s)

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Topic(s)

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Funding Scheme

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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

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 226 420,56
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.

No data

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