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HEiKA im Magazin lookKIT 2014/3
title lookKIT 14/3

Artikel über das HEiKA Projekt von Patric Meyer (Uni HD/ZI) und Björn Hein (KIT) im Forschungsmagazin lookKIT (2014/3, S. 68 ff).

Kontakt

HEiKA Geschäftsstelle

Dr. Regine Kleber and

María García

infoElu4∂heika-research de

Quantitative in vivo mapping and analysis of physiological H2O2 – dependent redox homeostasis in stem cells of the zebrafish central nervous system

Quantitative in vivo mapping and analysis of physiological H2O2 – dependent redox homeostasis in stem cells of the zebrafish central nervous system
Ansprechpartner:

Prof. Dr. Jochen Wittbrodt, contact
Centre for Organismal Studies (COS), Heidelberg University

Dr. Clemens Grabher, contact
Institute of Toxicology and Genetics (ITG), KIT

Projektgruppe:

Synthetic Biology

Partner:

Prof. Dr. Jochen Wittbrodt

Dr. Clemens Grabher

 

Starttermin:

01.01.2014

Endtermin:

31.12.2014

Reactive oxygen species, particularly H2O2, regulate essential physiological processes, including cell motility, cellular polarization and differentiation and in particular stem cell regulation. This regulatory modality relies on selective modification of thiol residues of target proteins.
How H2O2 selectively oxidizes thiolate-containing target proteins remains largely enigmatic. Moreover, our current knowledge of the redox changes that actually occur in the physiological whole-body context of living animals is very limited. We know little about the redox differences that exist naturally between the different tissues and cell types within the body. It also remains unclear to what extent in vivo redox states are influenced by behavioral and environmental factors, e.g., physical activity, circadian rhythm, nutrition or pollution. Our lack of knowledge is especially obvious with regard to the exact chemical nature of these changes, their subcellular origin, their spatiotemporal distribution, and their biological relevance.
In particular: What are the specific redox couples operating in a particular spatial and temporal context?
Here we will measure the activity and spatio-temporal distribution of specific redox couples in a vertebrate animal in vivo and investigate their biological function upon genetic and pharmaceutical manipulation. To this end we will generate a comprehensive 4D real-time map of developmental, physiological, pathophysiological and circadian H2O2 dependent redox homeostasis in the central nervous system of zebrafish larvae. The visualization of the in vivo spatio-temporal relationship between H2O2 signaling and the redox homeostasis of multiple thiol-switch sensor molecules in a living vertebrate animal (H2O2 levels and oxidative state of glutathione, peroxiredoxin and NADH) provide a valuable resource and will open up new opportunities for in vivo redox and stem cell biology.