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REDOXCYCLE SIGNED

The molecular interface between cell cycle and redox regulation

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EC-Contrib. €

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Project "REDOXCYCLE" data sheet

The following table provides information about the project.

Coordinator
TECHNISCHE UNIVERSITAET DRESDEN 

Organization address
address: HELMHOLTZSTRASSE 10
city: DRESDEN
postcode: 1069
website: http://www.tu-dresden.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 1˙499˙688 €
 EC max contribution 1˙499˙688 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    TECHNISCHE UNIVERSITAET DRESDEN DE (DRESDEN) coordinator 1˙499˙688.00

Map

 Project objective

Aberrant cell cycle and redox regulation are hallmarks of cancer. While cell cycle and redox signaling are extensively studied, it remains poorly understood how both communicate in physiological conditions. One reason is the emphasis on oxidative stress as a signature of cancer cells. Only recently, emerging evidence indicates that reactive oxygen species (ROS) also function as signaling molecules in physiological conditions, and that some of their key targets are cysteine residues on cell cycle proteins. This indicates that more subtle changes in redox signaling can affect proliferation and have the potential to promote cancer.

I propose to investigate how the cell cycle and redox homeostasis are coupled in a spatial-temporal manner and reveal the differences that distinguish physiological from pathological redox signaling. I will use genetic engineering to label endogenous cell cycle and redox proteins with fluorescent markers. I will measure relative and absolute molecule numbers of cell cycle and redox proteins, relate this to cell cycle and redox states, and determine the cysteines modified on cell cycle proteins. To functionally investigate the pathological potential of identified modifications I will use mammary 3D cell culture – a model that recapitulates many aspects of mammary architecture in vivo and is used to study early steps of breast tumorigenesis.

I expect our work to provide us with a quantitative description of the interface between cell cycle and redox regulation. Although intracellular cell behavior is never completely deterministic, a reasonable quantitative model should be predictive to some degree and reveal how different levels of ROS can affect cell cycle decisions. Shedding light on the cell cycle targets of ROS will indicate the nodes that can be hijacked by cancer cells. Together, this work will provide a significantly improved basis for our understanding of redox signaling in tumorigenesis and indicate new strategies for treatment.

 Publications

year authors and title journal last update
List of publications.
2018 Katrin Daniel, Jaroslav Icha, Cindy Horenburg, Doris Müller, Caren Norden, Jörg Mansfeld
Conditional control of fluorescent protein degradation by an auxin-dependent nanobody
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05855-5
Nature Communications 9/1 2019-10-09
2018 Rhys Grant, Ahmed Abdelbaki, Alessia Bertoldi, Maria P. Gavilan, Jörg Mansfeld, David M. Glover, Catherine Lindon
Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
published pages: 170272, ISSN: 2046-2441, DOI: 10.1098/rsob.170272
Open Biology 8/6 2019-10-09
2017 Thomas Zerjatke, Igor A. Gak, Dilyana Kirova, Markus Fuhrmann, Katrin Daniel, Magdalena Gonciarz, Doris Müller, Ingmar Glauche, Jörg Mansfeld
Quantitative Cell Cycle Analysis Based on an Endogenous All-in-One Reporter for Cell Tracking and Classification
published pages: 1953-1966, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.05.022
Cell Reports 19/9 2019-06-19
2017 Ezzaldin Ahmed Alfar, Dilyana Kirova, Judith Konantz, Sarah Birke, Jörg Mansfeld, Nikolay Ninov
Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-03873-9
Scientific Reports 7/1 2019-06-19
2017 Lilia Gheghiani, Damarys Loew, Bérangère Lombard, Jörg Mansfeld, Olivier Gavet
PLK1 Activation in Late G2 Sets Up Commitment to Mitosis
published pages: 2060-2073, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.05.031
Cell Reports 19/10 2019-06-19
2019 Anna K.L. Liess, Alena Kucerova, Kristian Schweimer, Lu Yu, Theodoros I. Roumeliotis, Mathias Diebold, Olexandr Dybkov, Christoph Sotriffer, Henning Urlaub, Jyoti S. Choudhary, Jörg Mansfeld, Sonja Lorenz
Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination
published pages: 1195-1210, ISSN: 0969-2126, DOI: 10.1016/j.str.2019.05.008
Structure 27(8) 2019-09-05
2018 Gábor Bakos, Lu Yu, Igor A. Gak, Theodoros I. Roumeliotis, Dimitris Liakopoulos, Jyoti S. Choudhary, Jörg Mansfeld
An E2-ubiquitin thioester-driven approach to identify substrates modified with ubiquitin and ubiquitin-like molecules
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07251-5
Nature Communications 9/1 2019-09-05
2019 Katharina B. Beer, Gholamreza Fazeli, Kristyna Judasova, Linda Irmisch, Jona Causemann, Jörg Mansfeld, Ann M. Wehman
Degron-tagged reporters probe membrane topology and enable the specific labelling of membrane-wrapped structures
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-11442-z
Nature Communications 10/1 2019-09-05

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