Biomolecular, Genomic and Bioinformatic Sciences Unit
Research at the Biomolecular, Genomic and Bioinformatic Sciences Unit (USBGB) is centered on the interdisciplinary field of Genomics. It includes Biochemistry, Molecular and Cell Biology, Genetics, Microbiology, Bioinformatics and Biostatistics as the main reference scientific disciplines.
The studies conducted by USBGB members range from Functional and Structural Genomics, including Evolutionary Genomics and Phylogenomics, to Systems Biology – an increasingly growing research area that combines all the most modern aspects of contemporary Biology, Molecular and Cellular Biotechnologies and Biomedicine, often with highly relevant applied implications and translational potential.
The research activity of the USBGB conjugates basic biological studies with more applied investigations in the fields of human health and biotechnology. Regarding basic biological research, most studies leverage model organisms in order to achieve an in-depth understanding of fundamental (and conserved) cellular processes, with the use of innovative bioinformatic, metagenomic, and molecular (e.g., transcriptomic) approaches. These touch upon all the main aspects of genetic information, including: genomes, genes and associated polymorphisms; gene expression (especially DNA transcription) and the regulatory processes (genetic and epigenetic) involved in its control; enzymes and structural proteins; also in relationship to cell/tissue functionality and its alteration under pathological conditions (e.g., chronic and/or degenerative diseases, neoplastic transformation and tumor progression, genotoxicity).
Special attention is paid to all the possible biomedical implications and translational potential of the basic research projects pursued by the USBGB, particularly with regard to the development and validation of novel recombinant HPV vaccines, synthetic single-chain antibody libraries, theranostic and immunotherapeutic agents; the discovery of specific protein-protein interaction inhibitors to be used as novel drugs (e.g., antibiotics) and the construction of innovative model systems aiding the study of important human (e.g., mitochondrial) pathologies and the identification of new small-molecule modifiers. Some research lines specifically related to ‘biotechnological innovation’ in the agro-food field are dedicated to the genetic improvement of industrial yeast strains, to the creation of novel probiotics and to the (bio)control of microbial toxins (e.g., aflatoxins).
Study of genes involved in the interaction and communication between natural vine strains of Saccharomyces cerevisiae through the use of cultural, genetic and genomic techniques.
BARUFFINI E., C. DALLABONA, C. DONNINI, T. LODI, P. GOFFRINI M
Molecular mechanisms of mitochondrial functions in yeast, widening the results to the study of human mitochondrial disorders. Expression and functional analysis in S. cerevisiae of potentially pathological mutations found in patients affected by mitochondrial diseases in order to evaluate their pathogenicity. Study of the molecular consequences of mutations. Search of molecules able to reverse or reduce phenotypic defects induced by these mutations by means of drug repositioning approaches or new drugs. Identification of the mechanisms of action and of the molecular target of the selected molecules. Use of different yeast models to study the effects (antioxidant, antimutagen on mtDNA, anti-aging) of natural and / or synthetic compounds.
Design and selection of recombinant ‘single-chain’ antibodies (‘nanobodies’) from combinatorial semi-random libraries built on an artificial universal scaffold. Development of different strategies for the functionalization/derivatization of synthetic nanobodies aimed at their utilization as high-performance immuno-diagnostic tools.
BOLCHI A., S. OTTONELLO
Design, physico-chemical characterization and functional validation of novel thermostable recombinant vaccines, produced also in the form of hyper-immunogenic nanoparticles, for preventive and therapeutic purposes. The main target has been the HPV minor capsid protein L2, but other antigens of diagnostic/prophylactic interest are also been pursued along with novel vaccine formulations (e.g., inhalable dry-powders).
Toxicological, geno-toxicological and epi-genotoxicological profile of environmental contaminants, pharmacologically active molecules and foods. Study of the structure / activity relationship of newly synthesized compounds with antitumor or antibiotic activity. Study of the relationship between genetic or epigenetic variants and onset / evolution of complex diseases (idiopathic infertility and ischemic pathologies).
De IASIO S.
Variations of the anthropometric traits in the Piedmontese and Emilian conscripts during the epidemiological transition, in the transition from the health system dominated by mortality to that characterized by morbidity. Determination of the health status of the nineteenth century military through the individual "fogli matricolari".
Research activity addresses different aspects of eukaryotic gene regulation through both mechanistic biochemical analysis and whole-genome approaches: i) ncRNA biogenesis and function; ii) transcriptomics of human retrotransposons in biology and disease; iii) epigenetic control of retrotransposon expression; iv) transcriptional control of yeast ribosome biogenesis
DONNINI C., M. MANFREDINI
Genetics and epigenetics of additive behavior. Identification, through statistical models of the Hazard Models type, of risk factors in the development of drug addiction, with particular attention to the role of genetic, epigenetic and environmental factors.
Development of separative analytical procedures for the determination, in mass spectrometry, of drugs (antibiotics, anti-HIV, anti-HCV) in human plasma samples.
Genetic improvement of yeasts for industrial fermentation. Selection of mutants high-producers of primary metabolites. Microbial fermentation for the recovery of industrial processing by-products.
The research interests is focused on the signaling pathways and molecular mechanisms involved in the resistance of both conventional and targeted anticancer therapies in hematologic malignancies, the design and effectiveness analysis of novel therapeutic strategies in in vitro ed in vivo pre-clinical cancer models.
Analysis of demographic processes in historical and contemporary populations: interactions between socio-economic, demographic and household variables. Studies on health and “living standards” in past populations
Development and optimization of a novel drug discovery platform based on ‘Bioluminescence Resonance Energy Transfer’ (BRET) performed in vivo in engineered yeast cells. Application of the BRET-based platform to the identification of protein-protein interaction inhibitors of biomedical interest; particularly, new antibacterial inhibitors.
MONTANINI B., S. OTTONELLO
Transcriptome analysis and other functional genomic approaches applied to the study of chronic viral human pathologies (HBV, HCV); to the discovery of novel biomarkers and potential drug targets in animal models of chronic and acute respiratory diseases; molecular characterization of proteotoxic stress models in yeast and the study of symbiotic filamentous fungi of marked environmental and commercial interest.
The study of overlapping genes, also called “dual-coding genes”, in viruses concerns their genealogy (which gene is ancestral and which gene is de novo), their peculiar nucleotide and amino acid composition and their mechanism of symmetric/asymmetric evolution
Function and evolution of catalytic biomacromolecules: protein enzymes, ribozymes (catalytic RNAs) and deoxyriboses (catalytic DNAs), and their applications. Studies on the enzymology and genomic distribution of enzymes dependent on the cofactor pyridoxal phosphate. Studies on the catalytic promiscuity of enzymes and on its contribution to the 'underground' metabolism.
Setting-up of novel functional assays, performed in engineered yeast and mammalian cells and based on the expression of amyloidotic proteotoxic polypeptides, for the functional identification of polyphenol human metabolites and other natural or synthetic compounds capable of promoting proteostasis while reducing cytotoxicity.
Gene functional predictions through Bio informatics and biochemical experiments. Big data for rare diseases.
Role of Glypican-5 proteoglycan in the control of tumor formation and progression through in vitro investigations and in mouse tumorigenesis models (including transgenic models). Role of NG2 / CSPG4 proteoglycan in the control of tumor formation and progression and as a target for the preclinical development of teranostic and immunotherapeutic agents. Development of new immunotherapeutic agents against haematological diseases through a "reverse immunoproteomics" approach.
Development of bio-control strategies for the containment of mycotoxins accumulation in food and feed commodities with a particular emphasis on the analysis of the regulatory mechanism involved in the control of aflatoxins biosynthesis and on morphological differentiation of Aspergillus flavus.
Protein-DNA interactions in bacterial transcription systems. Study of the bacterial nucleoid conformation by AFM and fluorescence microscopy. Study of the interaction of antitumor metal complexes with DNA. AFM imaging of pulmonary surfactants. Study of protein toxins produced by bacterial strains grown under stress conditions.
Investigation of the intestinal microbiota, using metagenomic and functional genomic approaches. Dissection of the biology of bifidobacteria and probiotic bacteria through genomic and functional genomic approaches using in vitro and in vivo models
Microbial genomics with specific interest on bifidobacteria and their interaction with the human host as well as with other members of the gut microbiota. Evaluation of the microbial composition and functionality of complex bacterial communities using metagenomics approaches in human, farming animals-companion animals as well as in various foods. Microbial bionformatics.