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The molecular basis of NleB-mediated bacterial virulence

Objective

Bacterial pathogens have evolved distinct ways of colonizing host cells and promote infection. Many human intestinal bacterial pathogens such as Salmonella, Shigella and enteropathogenic/ enterohemorrhagic Escherichia coli utilize type III secretion systems to deliver virulence effector proteins into the host to promote colonization and interfere with antimicrobial host response. Among the type III effectors, the NleB protein has been shown to be essential for virulence of enteric pathogens. NleB is a glycosyltransferase that has been shown to interact with host cell death-domain-containing proteins, GlcNAcylate a specific arginine on these and thereby inhibiting death receptor signalling and preventing host cell apoptosis. This proposal will 1) investigate how NleB specifically recognises the host death domains, 2) uncover the molecular mechanisms of arginine GlcNAcylation, 3) explain how death domain GlcNAcylation prevents the death domain from binding to its receptor, and 4) exploit this molecular information to generate bisubstrate inhibitors to interfere with this process.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

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-2014

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Coordinator

UNIVERSITY OF DUNDEE
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.

€ 183 454,80
Address
Nethergate
DD1 4HN Dundee
United Kingdom

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Region
Scotland Eastern Scotland Angus and Dundee City
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.

€ 183 454,80
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