Objective
The evolution of multicellular eukaryotic organisms correlates with an enormous increase of N- glycosites and N-glycoproteins, which have essential roles in cell-cell communication, organ development, the immune system, and other key functions in ontogenesis. At the core of this process stands oligosaccharyltransferase (OST), the central enzyme in protein N-glycosylation. OST glycosylates proteins that contain short recognition sequons (N-X-S/T) by transferring a well-defined glycan from a glycolipid substrate. These reactions occur in the endoplasmic reticulum and precede protein folding because most sequons are no longer accepted by OST in the folded protein.
To address how one enzyme, OST, can accommodate and process a multitude of acceptor proteins, we will combine structure determination of OST complexes by cryo-EM, chemo-enzymatic substrate synthesis, in vitro and in vivo analyses of the N-glycosylation reaction and output, and molecular modelling in our experimental approach.
Our research strategy is guided by the evolution of OST itself: In contrast to human cells, eukaryotic parasites have reduced the complexity of their N-glycoproteomes. This simplification correlates with a reduced complexity of OST architecture, which contains fewer than the 8 subunits of human OST. We plan to determine the first structures of parasite OST enzymes and compare their in vitro activities to human OST.
Based on the structural and functional differences between parasitic and human OST, we will search for specific small-molecule inhibitors of OST as research tools or as therapeutics.
Our studies will provide insight into N-glycoproteome biogenesis, reveal the functional architecture of mammalian and parasite OST enzymes, and facilitate the development of small- molecule OST inhibitors. The tools and methodologies developed will also pave the way for novel biotechnological applications of N-glycoprotein and N-glycopeptide generation through enzymatic in vitro pipelines.
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.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
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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.
8092 Zuerich
Switzerland
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.