Ricerc@Sapienza

Electrochemical biosensors provide an attractive means of analyzing the content of a biological sample due to the direct conversion of a biological event to an electronic signal. The signal transduction and the general performance of electrochemical biosensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale.

In multicellular systems, the control of cell size is fundamental in regulating the development and growth of the different organs and of the whole organism. In most systems, major changes in cell size can be observed during differentiation processes where cells change their volume to adapt their shape to their final function. How relevant changes in cell volume are in driving the differentiation program is a long-standing fundamental question in developmental biology.

Background: Phosphodiesterases (PDEs) are a superfamily of evolutionary conserved cyclic nucleotides (cAMP/cGMP) hydrolysing enzymes, components of transduction pathways regulating crucial aspects of cell life. PDE5, one of these families, is the molecular target of several drugs used to treat erectile dysfunction and pulmonary hypertension. Despite its medical relevance, PDE5 macromolecular structure has only been solved for the isolated regulatory and catalytic domains.

Improving the efficacy of gene therapy vectors is still an important goal toward the development of safe and efficient gene therapy treatments. S/MAR (scaffold/matrix attached region)-based vectors are maintained extra-chromosomally in numerous cell types, which is similar to viral-based vectors. Additionally, when established as an episome, they show a very high mitotic stability.

Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and miRNAs, long noncoding RNAs (lncRNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin-associated muscle-specific lncRNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo. In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein.

Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy.

In Pseudomonas aeruginosa, the ferric uptake regulator (Fur) protein controls both metabolism and virulence in response to iron availability. Differently from other bacteria, attempts to obtain fur deletion mutants of P. aeruginosa failed, leading to the assumption that Fur is an essential protein in this bacterium. By investigating a P. aeruginosa conditional fur mutant, we demonstrate that Fur is not essential for P. aeruginosa growth in liquid media, biofilm formation, and pathogenicity in an insect model of infection.

Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD.

Severe alpha?1?antitrypsin deficiency (AATD) is most frequently associated with the alpha?1?antitrypsin (AAT) Z variant (E342K). ZZ homozygotes exhibit accumulation of AAT as polymers in the endoplasmic reticulum of hepatocytes. This protein deposition can lead to liver disease, with the resulting low circulating levels of AAT predisposing to early?onset emphysema due to dysregulation of elastinolytic activity in the lungs. An increasing number of rare AAT alleles have been identified in patients with severe AATD, typically in combination with the Z allele.