Molecular physiology, regulatory mechanism and metabolic control in microbes

Regulation of transcription initiation plays a primordial role in the control of gene expression in Bacteria and Archaea. Even though Archaea are true Prokaryotes they differ considerably from the Bacteria and they constitute a separate Domain of Life, comprising also the most extremophilic microbes known today.

The archaeal information processing machineries (replication, transcription, translation) are even more closely related to the eukaryotic homologues. Interestingly, archaeal transcription exhibits a mosaic composition. The basal archaeal transcription apparatus is a simplified version of the eukaryotic Pol II system, but most of the archaeal transcription regulators are of the bacterial type.

Transcriptional regulation relies on protein-DNA, protein-ligand and protein-protein interactions which we aim to unravel and characterize at the molecular, atomic level. The approach is multidisciplinary: molecular physiology, genetics, molecular biology, physico-chemical and structural analyses are combined in integrated and convergent studies. As paradigms of complex transcriptional control mechanisms we investigate:

• regulation of the tandem pair of promoters in the E. coli carAB operon by arginine, pyrimidine and purine-specific signals and by global stringent control
• regulation of arginine metabolism in various bacteria, from psychrophiles to hyperthermophiles
• the mode of action of transcription regulators of the Lrp-family (Leucine responsive regulatory protein) from the hyperthermoacidophilic crenarchaeon Sulfolobus solfataricus