Research Programme

Presentation of the Research Programme

Research topics and long-term research goals

It is a novel concept to understand redox-regulation as a universal control element of signal transduction and to recognise it independently of oxidative stress. Principles of redox-regulation have the potential, similar to the fundamental control principal in phosphorylation/dephosphorylation, to coordinate cell function in a reversible manner.

Redox-regulation is increasingly appreciated as an element of cellular signal transduction. Similar to a posttranslational modification by phosphorylation, the redox-regulation is an essential communication principle in the network-based control of cellular functions. Here, redox-signals mediate a wide range of physiological responses, whereas a “derailment” of the redox-status can contribute to disease development in either a causal or epiphenomenological manner. In contrast to „oxidative stress“, the term „redox-regulation“ describes therefore a reversible and physiological reaction of the cell, in which the redox-signals are used in signal transduction.

In the here presented research network, the term redox-regulation is understood to include the regulation of signal transduction as consequence of oxygen availability and the formation of superoxide or nitric oxide and their metabolites respectively.
The thematic focus in the SFB-initiative are the generation of redox-active metabolites by NADPH-oxygenases and mitochondria as well as the altered rates of formation of NO and O2 and their interaction by regulation of expression and/or the activation of enzymes which generate NO or O2 or which have antioxidative effects. The aim is to discern the functional consequences of these physiological control mechanisms for essential cellular reaction such as proliferation, differentiation and cell integrity and to understand the influence of oxygen deprivation on these processes. Central questions are (i) how the basal oxidative tone contributes to the control of physiological cell functions, (ii) how redox-signals contribute to cellular protection mechanisms to protect cells from stress conditions, and (iii) how the reactions of NO and O2-, but also their interaction via specific reversible protein modifications or alterations in the proteome, contribute differentially to the control of redox-regulation.

Fig.1: Principles of redox-regulation

Cellular reactions such as activation of signal transduction and alteration of gene expression underlie redox-regulation resulting in a complex scheme of regulatory processes. Redox-modulators, such as oxygen concentration, the activity of antioxidative enzymes or products of ROS and NO, interefere with the the signal processing in regards to signal transduction or gene expression, respectively, but also via feed back mechanisms on the level of cell stimulation. This positive/negative feed back system allows to (re-)adjust the redox-status to ideally bring the cell into an optimal functional state.

Fig.1: Principles of redox-regulation