Control of gene expression represents the first level of genetic control. Key players in bacteria are transcriptional regulators and two-component signal transduction systems. These proteins have a dual function: they serve as sensors to recognize specific stimuli either within the cell or outside, and they activate or repress their target genes dependent on the absence or presence of these stimuli. In this way, they allow the cell to adapt to the prevailing conditions. We explore transcriptional regulators and two-component systems in selected microbial cell factories to elucidate their sensory properties, their target genes, and their mode of action (activation, repression). For this purpose, we analyse strains lacking or overexpressing the corresponding genes with respect to global gene expression (via DNA microarrays or RNAseq), we determine direct target genes (e.g. via ChAP-Seq), and we try to identify the stimuli of these regulators. In this way, we aim at a systemic understanding of the transcriptional regulatory network and at the same time provide biosensors for biotechnological applications (à link) and modules for new expression systems.
The activity of proteins can be controlled by a multitude of posttranslational modifications. We are interested in two types of modification, which are serine/threonine phosphorylation and pupylation. In Actinobacteria, the activity of the 2-oxoglutarate dehydrogenase complex is controlled by the phosphorylation status of an inhibitor protein (OdhI/GarA). We are studying the proteins of the signal transduction cascade controlling the phosphorylation status of the inhibitor protein. Actinobacterial pupylation resembles eukaryotic pupylation by tagging proteins for either degradation or other processes. We are particulary interested in the role of pupylation in iron homeostasis.