Presentation of the Research Program

Fig. 1:

Over the last years Redox-Regulation became a well-established regulatory principle of biological systems. Redox regulatory events like oxidation, nitrosylation, nitrosation or hydroxylation are reversible systems and thus, are clearly separated from oxidative stress, which is known to provoke irreversible changes. Posttranslational reversible protein modifications via redox signals constitutes a communication system to control cellular functions. The epiproteome, or more specifically the redox-proteome, detects changes in the oxygen level, the generation of reactive oxygen species, nitrogen species as well as of hydrogen sulfide and their multiple reaction products.

Redox-regulated processes affect (i) changes in enzyme activity or the DNA-binding capacity of transcription factors, (ii) aggregation of proteins, (iii) protein stability and/or function, and (iv) compartmentalization, cell-matrix and cell-cell communications, respectively. With these considerations the CRC 815 studies integrative processes such as cell differentiation, cell polarization, inflammation, pain, diabetes, electric conduction, and infection.

Fig. 2:

During the first funding period we focused on “Activation of Generating Systems”, i.e. NADPH-oxidases, respiratory chain complexes, prolyl hydroxylases, and cystatione γ-lyases. In the second funding period key aspects comprised “Investigations towards distinct effector structures” and functional consequences affecting inflammation, mitochondrial respiration, and the control of individual signaling complexes. The aim of the third funding period is to consolidate our knowledge of generating system and the epiproteome to further advance our understanding of the “Redox imprinting of biological systems”.

As redox imprinting of biological systems we define (i) methods to visualize redox events, like the identification of (bio-)markers linked to distinct generating systems, (ii) identification and mechanistic characterization of redox junctions in complex biological signaling cascades, (iii) the link between the epiproteome and metabolome, and (iv) questions approaching therapeutic options and generalizing our observations. In particular, the dynamic responses of molecular, cellular, and in vivo systems following the activation of generating systems, the temporal sequence of biological changes, and the reversibility will show how these systems are balanced, how they can be adjusted, and which functional redox-based consequences will result for cells, organs, and/or organisms. This might be linked to the onset of diseases but also healing processes. An integral part for the CRC is the analysis of posttranslational redox modifications within the proteome, using mass spectrometry (see also Redox-Proteomics)