Objective
Glutathione serves as the major thiol-redox buffer in the defense against Reactive Oxygen Species (ROS) in eukaryotes. Firmicutes bacteria utilize as thiol redox buffer bacillithiol (Cys-GlcN-Mal, BSH) and Actinomycetes produce the related redox buffer mycothiol (AcCys-GlcN-Ins, MSH). In eukaryotes, proteins are post-translational modified to S-glutathionylated proteins in response to oxidative stress. S-glutathionylation has emerged as major redox-regulatory mechanism and protects cysteine residues against overoxidation to sulfonic acids. Using thiol-redox proteomics and mass spectrometry (MS) we have recently discovered protein S-bacillithiolations as mixed BSH protein disulfides in response to oxidative stress in Firmicutes bacteria. Protein S-bacillithiolation controls the activity of the redox-sensing OhrR repressor and protects active site cysteine residues of metabolic enzymes, antioxidant function proteins and translation factors. However, it is unknown if ROS and infection conditions cause protein S-mycothiolations and affect the cellular MSH redox potential in pathogenic Mycobacteria and Corynebacteria. Here we aim to explore the comprehensive mycothiolome in the major respiratory pathogen Corynebacterium diphtheriae.
We apply gel-based and novel MS-based thiol-redox proteomic approaches for the quantitative analysis of the S-mycothiolome in C. diphtheriae under oxidative stress conditions (e.g. NEM-Biotin-Switch-Assay). Novel genetically encoded redox biosensors (Mrx1-roGFP2 and roGFP2-Orp1) will be developed for real-time imaging of the MSH redox potential and ROS production during infections in C. diphtheriae. The role of S-mycothiolated proteins for redox regulation, fitness, stress resistance and virulence mechanisms will be investigated. Our studies provide leads to understand the physiological role of thiol-redox switches in the defense against the host immune system and in the regulation of virulence mechanisms in Gram-positive pathogens.
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.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors biosensors
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine immunology
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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.
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.
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.
ERC-2013-CoG
See other projects for this call
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.
Host institution
14195 BERLIN
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.