Ricerc@Sapienza

Cell growth is regulated by coordination of both extracellular nutrients and intracellular metabolite concentrations. A large number of proteins receive signals from outside and orchestrate the intracellular response using nucleotides as second messengers. Unbalanced production, malfunction or changes in the stability of individual proteins cause pathologies.
In bacteria, biofilm formation is one of the most studied processes governed by nucleotide signalling. A key player in biofilm development is the cyclic dinucleotide c-di-GMP: environment triggers the activation of specific pathways to control c-di-GMP levels and to re-shape the energetic and metabolic profile of the cell. Given the huge impact of biofilms on human health, understanding the molecular details of c-di-GMP metabolism represents a critical step for the development of novel therapeutics against bacterial biofilms.

Very recently, in eukaryotes, the involvement of cyclic dinucleotides (CDNs), including the aforementioned c-di-GMP, in the innate immunity response has been established, through the activation of the inflammosome via the CDNs receptor STING. Prolonged inflammatory stress contributes to cellular transformation, which, in turn, involves a huge metabolic re-programming to sustain cell division (including the re-shaping of the energy and the one-carbon metabolism).
Therefore, as for bacteria, also in eukaryotes, CDNs sensing is undoubtedly associated to extensive metabolic reprogramming, whose molecular details controlling are yet to be defined.

Our major goal is to understand the structure and function of proteins at the interface between CDNs sensing and metabolism. We tackle this issue by studying various processes in prokaryotic and eukaryotic cells, including biofilm formation, host-pathogen interactions and metabolic reprogramming in cancer cells, both in hypoxia and normoxia, given the importance of hypoxia in both biofilm and cancer.