Quantitative in vivo Kartierung und Analyse der H2O2 - abhängigen Redox Homöostase im Zebrabärbling

• Antragsteller: Professor Dr. Uwe Strähle, seit 7/2015
• Fachliche Zuordnung: Biochemie und Physiologie der Tiere ; Zellbiologie
• Förderung: Förderung von 2014 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 251925061

Reactive oxygen species, particularly H2O2, regulate essential physiological processes, including cell motility, cellular polarization and differentiation but also more complex biological processes such as inflammation and regeneration. 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 spatio-temporal 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 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 biology.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1710: Dynamik thiolbasierter Redoxschalter in der Zellphysiologie
• Ehemaliger Antragsteller: Dr. Clemens Grabher, bis 3/2015