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Biomembrane bioenergetics system: functional mechanism and patophysiology

CNR personell: Nicola Altamura, Rosa Castaldo, Domenico De Rasmo, Paolo Lattanzio, , Rosa Lippolis, Domenico Marzulli.

Research associate: Sergio Papa

Research lines include the following:
1. Regulation of expression, structure and assembly of membrane energy transducing systems of both eukaryotes and prokaryotes.
The study of bioenergetics is gained interest in basic as well as clinical research for the crucial role played by mitochondria in the control of cellular events like cell growth, aging and apoptosis and, thus, in human diseases such as cancer and neurodegenerative disorders. In this contest, the signal transduction and second messengers, in particular cAMP, play an important role in regulating the biogenesis and functional capacity of membrane energy transducing systems and oxygen free radical balance in physiological and pathological conditions.
Another area involves the study of energy transducing systems in microorganisms 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 stop codon in mRNA leading to a premature arrest of translation. Functional consequences of premature termination codons (PTCs) include the degradation of PTCs-mRNA by the nonsense-mediated mRNA decay (NMD) pathway and synthesis of truncated proteins with loss of protein function. One approach to treat these disorders is based on the use of chemical agents that are able to suppress PTCs (read through) to restore the synthesis of a functional full-length protein. Searching for small compounds that are efficient in mediating read through is therefore highly demanded and requires an efficient screening system suitable for a high-throughput scale-

Research topics
The research activities concern:
Expression, structure and assembly of membrane energy transducing systems in mammalian cells in physiological and pathological conditions;
Cooperative allosteric mechanisms of energy transduction (cytochrome c oxidase proton pump);
Signal transduction and role of second messengers in the regulation of mitochondrial functions;
Study of the molecular pathogenic mechanisms in hereditary Parkinson’s disease and proliferative diseases;
Genomics and proteomics of energy transducing systems in human pathophysiology and microorganisms of industrial interest;
Characterization of the genes and their expression in antibiotic producing microorganisms terminal oxidases operon;
Study on factors involved in NMD regulation.
Development of reporter systems based on Saccharomyces cerevisiae for screening small compounds able to mediate read-through at the in-frame nonsense codons;
Yeast Saccharomyces cerevisiae as a genetic system for the expression of heterologous proteins of potential interest in biomedicine or industrial devices.

Cell systems and model organisms
Primary and immortalized mammalian cell lines.
Fibroblast cell cultures established by skin biopsy of subject affected by neurological disorders.
Cancer cell lines.
Microorganisms of interest in industry
Yeast Saccharomyces cerevisiae

Objectives
The general aim is the increase of knowledge on the mechanism of signal-dependent regulation of mitochondrial function in physiopathology. Extension of these findings will contribute to understand the role of mitochondria in the cellular and molecular events leading to cell degeneration providing to provide important perspectives in devising new therapeutic strategies.
Understanding how NMD is regulated. Combination of NMD inhibition with read through mediating compounds is a promising therapeutic approach alternate to gene therapy.

Address

Via Giovanni Amendola, 122/O
70126 Bari (BA) Italy

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