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Chemoenzymatic synthesis of complex glycans to decipher the interactions between them and Influenza A virus

Objective

Influenza A virus has two major envelope glycoproteins: HA and neuraminidase (NA). HA binds to sialic acid moieties of glycoconjugates of the host respiratory cells to initiate infection, whereas NA facilitates the release of progeny viruses from infected cells by cleaving sialosides. It is well documented that binding preference is a major determinant of influenza virus host range and avian viruses preferentially bind Neu5Acα(2,3)Gal, whereas human viruses bind Neu5Acα(2,6)Gal. This difference in specificity represents a barrier for transmission of avian viruses into humans. Glycan arrays have been used to assess influenza A virus receptor specificity. However, the currently available glycan arrays contain only a fraction of the glycans found on human airway epithelial cells and cannot uncover glycan binding specificities. Thus, we propose to develop an array that contains glycans representative of the structures found in human airways, since it is a priority in order to understand the biology of influenza virus transmission and pathogenesis. In addition, it has been described that there are two pathways by which influenza virus enters cells. It is believed that some N-glycans serve as attachment factors for concentrating virus particles on the surface of the host cells. However, only specific cell surface proteins modified by appropriate N-glycans can facilitate cell entry. The elucidation of the influenza virus receptor structure will unveil the mechanism at molecular level by which virus enters the cell. To this end, we will develop an experiment, which allows us to identify glycoprotein receptors of flu virus using cell surface glycan editing. The full comprehension of multi-branched glycans, along with the identification of the glycoproteins receptors of influenza virus, will allow the development of new and more efficient glycan-based therapeutics.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

UNIVERSITEIT UTRECHT
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.

€ 177 598,80
Address
HEIDELBERGLAAN 8
3584 CS Utrecht
Netherlands

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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.

€ 177 598,80
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