ChemAMPProject reference: 299740
Funded under :
Chemical AMPylomics: targeting a novel host-pathogen interaction
Total cost:EUR 209 033,4
EU contribution:EUR 209 033,4
Coordinated in:United Kingdom
Topic(s):FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development"
Call for proposal:FP7-PEOPLE-2011-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
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.
EU contribution: EUR 209 033,4
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