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Redox Relays SIGNED

Detecting, understanding and exploiting intracellular redox signaling relays

Total Cost €

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EC-Contrib. €

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Partnership

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 Redox Relays project word cloud

Explore the words cloud of the Redox Relays project. It provides you a very rough idea of what is the project "Redox Relays" about.

context    gene    und    composition    genetic    dissect    adaptations    signaling    channeled    signals    regulating    nitrogen    protein    proteins    sulfur    ubiquitous    glimpsed    unknown    living    redox    chains    adaptive    neighboring    oxygen    functional    nm    uncover    compartments    transcription    equivalents    cytosolic    species    iceberg    molecular    encoded    oxidants    screening    sphere    efficiency    behavior    manipulate    manipulation    supramolecular    relay    basic    unexplained    relayed    combination    reporters    thiol    tag    couple    proximity    mitochondrial    systematically    assemblies    asymp    cellular    oxidizing    solution    resilience    manner    strategy    yield    observation    endogenous    tools    fundamental    transmission    monitor    conundrum    modify    operate    mediated    genetically    proteomics    links    thiols    suggests    relays    mechanisms    specificity    profiling    tip    peroxidases    cell    organismal    give    regulation    dynamically    genes    found    metabolism    assemble    reactive    reversibly    sense    insights    precision    healthspan    vivo    coding    h2o2    nuclear    largely   

Project "Redox Relays" data sheet

The following table provides information about the project.

Coordinator
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG 

Organization address
address: IM NEUENHEIMER FELD 280
city: HEIDELBERG
postcode: 69120
website: www.dkfz.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙006˙250 €
 EC max contribution 2˙006˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG DE (HEIDELBERG) coordinator 2˙006˙250.00

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 Project 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.

 Publications

year authors and title journal last update
List of publications.
2018 Daria Ezeriņa, Yoko Takano, Kenjiro Hanaoka, Yasuteru Urano, Tobias P. Dick
N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production
published pages: 447-459.e4, ISSN: 2451-9456, DOI: 10.1016/j.chembiol.2018.01.011
Cell Chemical Biology 25/4 2019-06-11
2018 Sarah Stöcker, Michael Maurer, Thomas Ruppert, Tobias P Dick
A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation
published pages: 148-155, ISSN: 1552-4450, DOI: 10.1038/nchembio.2536
Nature Chemical Biology 14/2 2019-06-11

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