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REDOXCYCLE SIGNED

The molecular interface between cell cycle and redox regulation

Total Cost €

EC-Contrib. €

Partnership

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REDOXCYCLE project word cloud

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

deterministic oxygen hijacked vivo markers manner cysteines genetic shedding cycle differences spatial coupled stress residues 3d redox decisions significantly never regulation functionally predictive treatment engineering cells behavior indicates subtle poorly modified reactive oxidative architecture distinguish molecule cysteine physiological reasonable relative strategies nodes proteins intracellular quantitative basis molecules species absolute ros degree endogenous extensively proliferation completely interface modifications hallmarks emphasis cell culture tumorigenesis pathological label recapitulates model communicate relate homeostasis breast indicate temporal light levels signaling signature fluorescent cancer description aberrant function mammary reveal

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 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.	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

List of publications.
year	authors and title	journal	last update
2018	Katrin Daniel, Jaroslav Icha, Cindy Horenburg, Doris MÃ¼ller, Caren Norden, JÃ¶rg 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, JÃ¶rg 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 MÃ¼ller, Ingmar Glauche, JÃ¶rg 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, JÃ¶rg 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, BÃ©rangÃ¨re Lombard, JÃ¶rg 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, JÃ¶rg 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	GÃ¡bor Bakos, Lu Yu, Igor A. Gak, Theodoros I. Roumeliotis, Dimitris Liakopoulos, Jyoti S. Choudhary, JÃ¶rg 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, JÃ¶rg 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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