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Chemical AMPylomics: targeting a novel host-pathogen interaction

Objectif

In 2009 protein AMPylation, the reversible post-translational adenylation of target proteins with adenosine monophosphate (AMP), was first revealed as a novel mechanism for pathogenic bacteria to target and disrupt interactions of host GTPases with their cognate binding partners. Furthermore, there is growing evidence that AMPylation also operates as a general intracellular signaling mechanism in normal cell function. This novel post-translational modification is catalyzed by AMP transferases containing a so-called Fido motif that has been found across prokaryotes and eukaryotes, in over 2700 putative bacterial and mammalian proteins. Consequently, AMPylation is rapidly emerging as a fundamental mechanism to regulate protein-protein interactions and cell signaling in normal cells and in host-pathogen interactions, providing an opportunity for the discovery of new biology and targets for new antibiotics with novel mode of action. However, without robust tools to identify and manipulate both AMP transferases and their AMPylated protein substrates, our understanding of this complex signaling network will remain superficial.
This Fellowship project aims to develop and apply chemical probes and technologies that will enable for the first time high-throughput analysis and exploration of the complex biological networks involved in protein AMPylation. These chemical tools will be applied to mapping the changes in AMPylation that occur during bacterial infection in the host and the pathogen, with the ultimate objective of identifying and validating cellular mechanisms that can be targeted for future antimicrobial therapy.

Appel à propositions

FP7-PEOPLE-2011-IEF
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Coordinateur

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Contribution de l’UE
€ 209 033,40
Adresse
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Royaume-Uni

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Région
London Inner London — West Westminster
Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Brooke Alasya (Ms.)
Liens
Coût total
Aucune donnée