Görke

Our research aims to unravel novel principles underlying signal-perception, -transduction and cellular regulation in the model organism Escherichia coli. Mechanistically, we focus on the roles of small regulatory RNAs (sRNAs), mechanisms achieving specificity in RNA turnover and on the functions of protein-protein interaction for regulation.

In a first project, we investigate the roles of RNase adaptor proteins for

Our research aims to unravel novel principles underlying signal-perception, -transduction and cellular regulation in the model organism Escherichia coli. Mechanistically, we focus on the roles of small regulatory RNAs (sRNAs), mechanisms achieving specificity in RNA turnover and on the functions of protein-protein interaction for regulation.

In a first project, we investigate the roles of RNase adaptor proteins for regulated turnover of transcripts. We recently identified a novel regulatory circuit, composed of two small RNAs and the RNA binding protein RapZ, which controls synthesis of the cell wall biosynthesis enzyme GlmS (Fig. 1). When synthesis of cell wall metabolites such as glucosamine-6-phosphate (GlcN6P) is required, the small RNA GlmZ base-pairs with the glmS mRNA thereby activating translation. The latter process is assisted by the hexameric RNA chaperone Hfq, which promotes base-pairing. In contrast, when dispensable, GlmZ is targeted to degradation by endoribonuclease RNase E. This process requires protein RapZ, which binds GlmZ and recruits RNase E through protein-protein interaction. Degradation of GlmZ is antagonized by a homologous small RNA, GlmY, which acts as decoy and sequesters protein RapZ, if cell wall biosynthesis shall occur (Fig. 1). RapZ is the first discovered protein shown to serve as an adaptor to mediate decay of a specific transcript by a globally acting RNase. We speculate that there exist many more proteins like RapZ explaining how specificity in RNA decay can be achieved. Currently, the identification and characterization of such adaptors is a major task in our laboratory. In addition, we clarify the mechanistic details underlying the GlmY-GlmZ-RapZ circuit and try to exploit this mechanism for antimicrobial chemotherapy.

Furthermore, we investigate the mode of operation of histidine sensor kinases, which represent the primary sensory systems of bacteria. The usually membrane bound kinases sense specific signals in the environment and transduce the gained information into the cell leading to changes in gene expression or of other cellular activities. We previously identified an accessory protein named PtsN, which modulates the activities of histidine kinases from inside the cell through direct interaction (Fig. 2). We study how PtsN achieves this task and investigate the physiological meaning of this additional layer of regulation of kinase activities.