Cyanobacteria are oxygenic phototrophs that assimilate CO₂ into organic compounds. For CO₂ fixation at low ambient concentrations, cyanobacteria evolved a carbon concentrating mechanism that employs high affinity inorganic carbon transporters. Recently, we identified the PII-like protein SbtB as potential CO₂-sensing module. Similar to nitrogen-regulatory PII proteins, SbtB is able to bind adenine nucleotides, but unlike these, it binds preferentially the second messenger cAMP. An SbtB-deficient mutant is severely impaired in the acclimation to varying CO₂ levels. The modulation of adenylate cyclase activity by bicarbonate has been often discussed as potential carbon-sensing system among cyanobacteria, however, the physiological relevance was enigmatic.
Here, we hypothesize that SbtB represents a new sensor for inorganic carbon availability by responding to the second messenger cAMP. The aim of this proposal is to unravel the second messenger signaling network around SbtB in the cyanobacterial model strain Synechocystis sp. PCC 6803.

The stringent response is characterised by the synthesis of the messenger molecule (p)ppGpp, which interferes with many cellular processes, including transcription, replication and translation. The phenotypic consequences resulting from (p)ppGpp accumulation vary among species and can be mediated by different underlying mechanisms. We elucidated major players and mechanisms of the stringent response in Staphylococcus aureus. In S. aureus the stringent response plays important roles in virulence, phagosomal escape and antibiotic tolerance.

We aim to unravel the molecular mechanisms and functional consequences of (p)ppGpp-dependent gene activation.

We identified the stringent response as part of heat stress response during thermotolerance in B. subtilis. We hypothesize that the known activities of stringent response, which result in down regulation of translation, cell growth and DNA replication, is an intricate and important part of heat stress response, because curbing new protein synthesis will lower the load on the cellular protein quality control system.

Using various techniques and different experimental approaches we want to elucidate the role of the second messenger (p)ppGpp and its synthesizing and degrading enzymes during stringent and heat stress response in B. subtilis cells.

(p)ppGpp is a widespread second messenger best known as alarmone that alerts the cell to starvation conditions and leads to major re-arrangements in bacterial physiology. However, the signaling molecule affects numerous other pathways, among them the growth-rate controlled proteolysis of LpxC, an essential enzyme for lipopolysaccharide biosynthesis.

The project aims at the identification of ppGpp-binding proteins with a focus on enzymes involved in LPS and phospholipid biosynthesis. Overall, we expect to provide new insights into the comprehensive role of ppGpp in physiological adaptations of E. coli.

The stringent response (SR) is a central bacterial adaptation mechanism, mediated by the nucleotide-based second messengers, (p)ppGpp. The RelA protein translates amino acids limitation into a (p)ppGpp signal to adapt the bacterial metabolism. RelA possesses a strong ribosome-dependent (p)ppGpp synthetic activity that is activated by amino acid starvation via direct sensing of the deacylated tRNA in the ribosomal A-site. In our project, we aim at an in-depth mechanistic and structural understanding of RelA and its functional role during the SR.