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Content archived on 2024-06-18

THE ROLE OF O-GlcNAc IN BACTERIAL SIGNAL TRANSDUCTION AND VIRULENCE

Objective

O-GlcNAc modification of specific serines/threonines on intracellular proteins in higher eukaryotes has been shown to directly regulate important processes such as the cell cycle, insulin sensitivity and transcription. This dynamic modification, which shows interplay with protein phosphorylation, is regulated by two counteracting proteins, which catalyse transfer of GlcNAc from UDP-GlcNAc to specific serines/threonines on protein substrates (by O-GlcNAc transferase) and the subsequent hydrolysis (by O-GlcNAcase). Disruption of O-GlcNAc levels within the cell has been shown to be associated with neurodegenerative diseases, cancer and diabetes. Despite recent biochemical and structural advances in the O-GlcNAc field, our understanding of the precise functional implications of O-GlcNAc is still limited. Furthermore, we do not understand how O-GlcNAc transferase and O-GlcNAc hydrolase, recognise protein substrates and achieve selectivity.
Interestingly, O-GlcNAc modification of proteins is not restricted to higher organisms. It is now emerging that bacteria, in particular pathogenic bacteria, are able to glycosylate a range of proteins. Many pathogenic bacteria that either have the ability to penetrate and replicate, or inject virulence factors in the host cells, thus disrupting the normal function of the host proteins within the cell. Furthermore, preliminary data suggests that some bacteria glycosylate their own proteins within the cell. With the help of the Marie Curie International Reintegration Grant, I aim to experimentally test the hypothesis that some of these O-GlcNAc modifying proteins are secreted bacterial virulence factors, targeting specific proteins in the host cell. In addition, I intend to investigate bacteria that can O-GlcNAc modify their own intercellular proteins. Thus, both types O-GlcNAc modifications provide an attractive target for therapeutic intervention against bacterial pathogens.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2010-RG
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Funding Scheme

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MC-IRG - International Re-integration Grants (IRG)

Coordinator

UNIVERSITY OF DUNDEE
EU contribution
€ 100 000,00
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.

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