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Unravelling protein phosphorylation mechanisms and phosphoproteome changes under nitrosative stress conditions in E.coli

Project description

Protein phosphorylation and nitrosative stress conditions in E. coli

The fight against global antibiotic resistance is complicated by the slow development of more effective therapeutic solutions. Protein phosphorylation (PP) emerged recently as one of the major post-translational modifications in bacteria, involved in the regulation of multiple physiological processes. The EU-funded NOPHOS project aims to uncover the unknown regulatory role of PP in prokaryotes involved in nitrosative stress (NS) detoxification in the bacterial E. coli model. Researchers propose to examine global protein modifications (phosphoproteomics) under NS and characterise PP in individual proteins involved in NS response. The goal is to construct a network model that reflects the phosphoproteomic changes during NS in E. coli, enabling the design of new bacterial targets.

Objective

Currently, we face a global antibiotic resistance crisis aggravated by the slow development of more effective and anti-resistance promoting therapeutical solutions. Protein phosphorylation (PP) has recently emerged as one of the major post-translational modification in bacteria, involved in the regulation of multiple physiological processes. In this MSCA individual fellowship application we aim to bridge the current gap in the field for prokaryotes by unravelling the unknown regulatory role of PP on proteins involved in nitrosative stress (NS) detoxification in the model bacterium E.coli. We propose to examine for the first time both global protein modifications (e.g. phosphoproteomics) under nitrogen species stress, as well as characterize PP in individual proteins involved in NS response. We will construct a network model that reflect the phosphoproteomic changes upon NS in E.coli that may pave the way for the design of new bacterial targets. Understanding how bacteria respond to the chemical weapons of the human innate system is fundamental to develop efficient therapies. We will pioneer research on the mechanism and the regulation of nitric oxide detoxification proteins already identified as phosphorylated, by analyzing how this modification influences their stability and activity in vitro and in vivo. This project opens up new research paths on bacterial detoxification systems and signalling in general, addressing for the first time the role of PP in these processes. The proposal brings together transversal and scientific skills that will enable the researcher to lead the development of this emerging field and position herself as an expert in the area, and aims at establishing the importance of PP in NO microbial response, a novelty in this field.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-WF-2018-2020

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Coordinator

UNIVERSIDADE NOVA DE LISBOA
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.

€ 147 815,04
Address
CAMPUS DE CAMPOLIDE
1099 085 Lisboa
Portugal

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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.

€ 147 815,04
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