Project description
Redefining glycosylation
Glycosylation is a common post-translational modification associated with the addition of sugar molecules to proteins. This process affects protein folding and function and was traditionally believed to take place only in the secretory pathway. However, recent evidence suggests that glycosylation can also occur inside the nucleus. The ERC-funded SWEETSWAP project aims to investigate the idea that extended glycosylation also takes place inside mammalian nuclei. Researchers will employ a multidisciplinary approach to identify nuclear glycans and uncover how they are made as well as their role in gene expression regulation. Project results could redefine cell biology and open new directions for understanding disease mechanisms.
Objective
Glycosylation is the most common post-translational modification (PTM), decorating two thirds of secreted human proteins. Often dysregulated in disease, the specific attached glycan influences folding and function. Extended glycosylation is supposed to exclusively occur in the secretory pathway. I propose that this model needs to be revised. My preliminary results—both computational and experimental—question this long-standing dogma and hint at a new kind of PTM: extended glycosylation in mammalian nuclei. I propose a research project that exhaustively determines the presence, biosynthesis, transport, and function of extended nuclear glycosylation as a new group of PTMs. This ambitious project will broaden the areas of cell biology that are modulated by glycosylation, launching many new inquiries into disease-relevant functions of glycans, such as gene expression regulation via glycosylation, beyond the known case of O-GlcNAc. I will measure and probe nuclear glycosylation with a broad array of computational and experimental methods, such as subcellular glycoproteomics, glycomics, glyco-CLIP, data mining, AI, genetic engineering, click chemistry, immunostaining, flow cytometry, and CRISPR/Cas9 knockout screens. My approach is structured into three main aims: (i) rigorously cataloguing which nuclear glycan structures are exposed on which proteins in which cell line/species, delineating a nuclear glycome, (ii) elucidating mechanistically how these molecules are biosynthesized and transported into the nucleus, and (iii) probing the functions of these novel PTMs in human cells. Each aim will further the central hypothesis of nuclear glycosylation and has planned experiments to address aspects from biosynthesis to function. Crucially, this research will resolve several curious observations from decades of glycobiology, leading to the rewriting of textbooks, and open up a new field of study with the function of glycans in nuclear processes.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences biochemistry biomolecules carbohydrates
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Call for proposal
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(opens in new window) ERC-2025-STG
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405 30 Goeteborg
Sweden
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