Focus

Biomembrane bioenergetics system: functional mechanism and pathophysiology

1. Regulation of expression, structure and assembly of mem¬brane energy transducing systems of both eukaryotes and prokaryotes.
In this contest, the signal transduction and second messen¬gers, in particular cAMP, play an important role in regulating the biogenesis and functional capacity of membrane ener¬gy transducing systems and oxygen free radical balance in physiological and pathological conditions. Another area in¬volves the study of energy transducing systems in microor¬ganisms of industrial interest. Particularly significant results have been obtained concerning structure and functional mechanisms of mitochondrial and bacterial cytochrome c oxidase and ATP synthase.
2. Many genetic diseases, including some forms of cancer, are caused by nonsense mutations that generate in-frame premature termination codons (PTC). PTCs cause a prema¬ture arrest of translation and activate nonsense-mediated mRNA decay (NMD), a process that specifically recogniz¬es and degrades PTCs-containing mRNA, with consequent loss of protein function. To date there is no genetic therapy available for these disorders. One approach, called "sup¬pression therapy" is based on chemical-induction of sup-pression at PTCs (read-through), but not at the natural stop codon. Searching for small compounds able to suppress PTCs and/or modulate NMD to restore the synthesis of a functional full-length protein is highly demanded and re¬quires development of efficient screening systems suitable for a high-throughput scale.