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Detecting, understanding and exploiting intracellular redox signaling relays

Objective

Redox signaling is a process by which endogenous oxidants, derived from metabolism, reversibly modify particular thiols on particular proteins to change their functional behavior in an adaptive manner. However, the molecular mechanisms of redox signaling remain largely unknown. In particular, specificity and efficiency of redox signaling remain unexplained. The now emerging solution to this conundrum is that redox signaling is mediated and channeled by protein-to-protein redox relay chains that dynamically assemble in the cytosolic, nuclear and mitochondrial compartments. We and others have found that H2O2 signals are relayed through thiol peroxidases to neighboring proteins within supramolecular assemblies. Evidence now suggests that so far we have just glimpsed the ‘tip of the iceberg’, namely that redox relay chains are ubiquitous and also operate for reactive nitrogen and sulfur species. This project aims to systematically uncover, dissect, monitor and manipulate the redox relay chains that give specificity and efficiency to redox signaling. The basic strategy is to tag all protein-coding genes with genetically encoded reporters which –within the context of the living cell– sense the transmission of thiol oxidizing equivalents within their sphere of immediate proximity (≈10 nm). A combination of genetic screening, redox proteomics and transcription profiling will then allow to identify the composition of redox relays, their endogenous target proteins und their functional impact on gene regulation. The knowledge about the composition of redox relays will lead to precision tools for the observation and manipulation of defined redox signaling pathways in vivo. The project is expected to yield fundamental insights into the specific molecular links by which reactive oxygen, nitrogen and sulfur species couple changes in metabolism to cellular and organismal adaptations regulating resilience and healthspan.

Fields of science (EuroSciVoc)

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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)

Programme(s)

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Topic(s)

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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.

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.

(opens in new window) ERC-2016-ADG

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Host institution

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
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.

€ 2 006 250,00
Address
IM NEUENHEIMER FELD 280
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
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.

€ 2 006 250,00

Beneficiaries (1)

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