Objective
Ubiquitination represents one of the most versatile post-translational modifications in eukaryotes and is involved in regulation of numerous cellular processes. Despite prokaryotes lacking this system, facultative intracellular bacteria like Salmonella, Shigella and Legionella have evolved multiple strategies to manipulate the host ubiquitin (Ub) system to their own benefit. This proposal is focussed on gaining a fundamental understanding of the Ub system in the course of bacterial infections. We will employ advanced quantitative proteomics to perform a global analysis of the dynamic changes in the ubiquitinome and phosphoproteome of epithelial cells and macrophages upon infection with Salmonella, Shigella and Legionella. The comprehensive datasets will constitute an invaluable resource freely available to the scientific community. We expect to identify novel pathways triggered by selected bacterial ligases and will characterise their contribution to pathogenicity and virulence, as well as their suitability for being targeted in a therapeutic setting. Both medicinal chemistry and structural biology approaches will be exploited to identify inhibitors for NEL-type bacterial ligases. Hypothesis-driven projects within the work program focus on (i) a novel chemical modification of Ub controlling Legionella infections and (ii) the observation that Ub chains on Salmonella can form nanoscale clusters that recruit and activate multiple signalling pathways within the host cell. Super-resolution microscopy and single-molecule imaging will be used to visualise and dissect these Ub-triggered complexes.
Taken together, the combination of unbiased global proteome analysis and hypothesis-driven projects creates a unique scientific program within the biomedical field of understanding and combatting bacterial infections. Along the same lines, this proposal holds a great potential for the future development of novel strategies for antibacterial therapies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine medicinal chemistry
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences molecular biology structural biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
ERC-ADG - Advanced Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2016-ADG
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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.
60323 FRANKFURT AM MAIN
Germany
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.