SFB 815:  Redox-Regulation: Generating Systems and Functional Consequences

Subject Area Medicine
Biology
Term from 2009 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 61867463
 

Project Description

Redox-regulated processes are positioned at the interface between genome coded structure/function relationships and their adaptation to the availability of oxygen, the generation of superoxide, nitric oxide, and hydrogen sulfide as well as their metabolites. In analogy to the add-on of the epigenome to the genome we have to expand the proteome by the epiproteome, or more specifically the redox-proteome. The posttranslational reversible protein modification via redox signals constitutes a communication system to control cellular functions. 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 Collaborative Research Centre (CRC) studies integrative processes such as cell differentiation, cell polarization, inflammation, pain, diabetes, electric conduction, and infection. 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-imprints, like the identification of (bio-)markers in relation 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. At an interdisciplinary level the CRC aims at contributing and understanding the imprinting of cardiovascular, oncological/immunological, and neurological systems by identifying and modulating redox-signatures. A detailed knowledge and an appreciation on general concepts towards redox-networks should enable others to use our findings and apply them to future question in biomedicine.
DFG Programme Collaborative Research Centres

Completed projects

Applicant Institution Goethe-Universität Frankfurt am Main
Spokesperson Professor Dr. Bernhard Brüne