- Yeast as a model system for mitochondrial diseases. Understanding the biology of complex systems is facilitated by comparing them with simpler organisms. Budding yeasts provide ideal model system for eukaryotic cell biology; yeast genetics offer unique tools for discovering gene function and defining genetic networks starting from a single mutant. Hundred of nuclear genes are involved in biogenesis and in maintenance of the mitochondrial DNA in the yeast Saccharomyces cerevisiae; most of them possess a human orthologue. All these reasons have contributed to make S. cerevisiae a particularly suitable organism for the study of mitochondrial disorders. The main objective of our research is to use S. cerevisiae as a model to investigate the molecular bases underlying the pathogenic mechanisms of human mitochondrial diseases.

- Researches about regulation of fermentative/oxidative metabolism in yeast (Saccharomyces cerevisiae and Kluyveromyces lactis) with particular attention to carbon sources utilization. Carbon source uptake and its regulation are studied by genetic and genomic approaches. Genes encoding carbon source permeases are characterized by construction of deletion mutants and by genomics and phylogenetic analysis in several Ascomycetes. This subject is important both in fundamental and applied research, expecially in agronomic and food fields (es. in the production of fermented food, like wine, beer, baked products) and for heterologous protein production..

- Research projects of Plant Genetics Unit - Genetics and molecular physiology of ammonia assimilation in plants with a peculiar emphasis on the role of the enzyme glutamate dehydrogenase in N/C balance and on the effect of abiotic stresses. For this purpose, different mutants ( antisense, overexpressors, T-DNA tagged) of Nicotiana plumbaginifolia and Arabidopsis thaliana, displaying modified levels of GDH activity have been obtained in our lab. Our goal is to increase our knowledge on the role of the enzyme comparing the behaviour of wt and mutant lines in response to different treatments that may trigger the activity of homeostatic mechanisms operating at different levels of plant structure (organs, tissues, cells, subcellular organs). - Development of molecular assay for the diagnosis of micotoxin producer fungi in food commodities. This research project is part of a framework in which the different partners are committed to evaluate the reliability of control and safety procedures during feed and/or food storage and processing. Our task has the purpose of collecting data on the regulation of the expression of genes belonging to the aflatoxin gene cluster in order to develop a set of molecular markers to be used as diagnostic assay for aflatoxin producer strains

- The research unit of “ Environmental mutagenesis and genetic toxicology “ works out plans related to: - genotoxicity properties of new drugs utilizing cito- and genotoxicity tests in different organisms and human cell lines during the planning stage of biologically active chemicals; - correlations among genetic polimorphisms and resistance/sensititvity to drugs and xenobiotics related to diet or work environment; - assesment of mutagen or antimutagen properties of chemicals present in foodstuffs and genotoxicity monitoring of complex mixtures (air, water and soil) by mutagenicity tests.

- The Research Unit “Human Genetics” is interested in studying Behavioural Genetics and Pharmacogenetics of addictions and their treatments. Drugs dependence and abuse is a complex disorder that involves multiple genetic factors, not all identified, environmental factors and gene-gene and gene-environment interactions. The aim of the research is to identify: i. which variation in specific genes make some individuals vulnerable/relatively resistant to addiction and, ii. environmental factors/experiences that could represent protection factors. Further aim of the research is the identification of genes variants that determine variable response to the treatments to develop novel aimed pharmacotherapies.

- Biodiversity of the bacterial communities by genetic and genomic approach. Our research activities have entailed the use of genomic approaches to improve the understanding of the biodiversity of the bacterial communities residing in the human gut and the scientific basis of their interaction with the host. The overall aim of the program is to provide avenues for improvement and identification of health promoting bacteria, also called probiotics, through genomic (probiogenomics) and post-genomic analyses.

• DNA Sequencing

• Site Directed Mutagenesis

• Gene Disruption

• Gene expression Analysis: Northen, RT-PCR

• Gene Cloning

• Transient and stable gene expression in plants

• RNA antisense technology inplants

• Mutagenicity testing: Single cell gel electrophoresis (Comet assay)

• Mutagenicity testing: Bacterial reverse mutation test (Ames test); Cytokinesis-block micronucleus assay; Mitochondrial mutability, Gene conversion, mitotic crossing over and reversion assays in Saccharomyces cerevisiae.

• General toxicity: MTT and MTS proliferation assay; Luminescent cell viability assay; Ethidium bromide/Hoechst 33342 cell viability assay.

-Panizza, E., Ercolino, T., Mori, L., Rapizzi, E., Castellano, M., Opocher, G., Ferrero, I., Neumann, H.P., Mannelli, M., Goffrini, P. Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome. Hum Mol Genet 2013; 22 804-15.

-  Baruffini, E., Dallabona, C., Invernizzi, F., Yarham, J.W., Melchionda, L., Blakely, E.L., Lamantea, E., Donnini, C., Santra, S., Vijayaraghavan, S., Roper, H.P., Burlina, A., Kopajtich, R., Walther, A., Strom, T.M., Haack, T.B., Prokisch, H., Taylor, R.W., Ferrero, I., Zeviani, M., Ghezzi, D. MTO1 Mutations are Associated with Hypertrophic Cardiomyopathy and Lactic Acidosis and Cause Respiratory Chain Deficiency in Humans and Yeast. Hum Mutat 2013; 34 1501-9.

-  Turroni, F., Serafini, F., Foroni, E., Duranti, S., O’Connell Motherway, M., Taverniti, V., Mangifesta, M., Milani, C., Viappiani, A., Roversi, T., Sánchez, B., Santoni, A., Gioiosa, L., Ferrarini, A., Delledonne, M., Margolles, A., Piazza, L., Palanza, P., Bolchi, A., Guglielmetti, S., van Sinderen D., and Ventura, M.. The role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2013; 110(27):11151-6.

- Buschini A, Villarini M, Feretti D, Mussi F, Dominici L, Zerbini I, Moretti M, Ceretti E, Bonfiglioli R, Carrieri M, Gelatti U, Rossi C, Monarca S, Poli P. Multicentre study for the evaluation of mutagenic/carcinogenic risk in nurses exposed to antineoplastic drugs: assessment oa DNA damage. Occup Environ Med. 2013;70:789-94.

-  Haack, T.B., Kopajtich, R., Freisinger, P., Wieland, T., Rorbach, J., Nicholls, T.J., Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M., Mayr, J.A., Prokisch, H. ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet . 2013

-Indrieri, A., Conte, I., Chesi, G., Romano, A., Quartararo, J., Tatè, R., Ghezzi, D., Zeviani, M., Goffrini, P., Ferrero, I., Bovolenta, P., Franco, B. The impairment of HCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes. EMBO Mol Med 2013; 5 280-93.

-Invernizzi, F., Tigano, M., Dallabona, C., Donnini, C., Ferrero, I., Cremonte, M., Ghezzi, D., Lamperti, C., Zeviani, M. A Homozygous Mutation in LYRM7/MZM1L Associated with Early Onset Encephalopathy, Lactic Acidosis, and Severe Reduction of Mitochondrial Complex III Activity. Hum Mutat. 2013; .

- Turroni, F., Peano, C., Pass, D., Foroni, E., Severgnini, M., Claesson, M., Kerr, C., Hourihane, J., Murray, D., Fuligni, F., Gueimonde, M., Margolles, A., De Bellis, G., O’Toole, P.W., van Sinderen, D., Marchesi, J., and Ventura, M.. Diversity of bifidobacteria within the infant gut microbiota. PloS One 2012; 7(5):e36957.

-Alston, C.L., Davison, J.E., Meloni, F., van der Westhuizen, F.H., He, L., Hornig-Do, H.T., Peet, A.C., Gissen, P., Goffrini, P., Ferrero, I., Wassmer, E., McFarland, R., Taylor, R.W. Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. J Med Genet 2012; 49 569-77.

- Ferrarini L, Pellegrini N, Mazzeo T, Miglio C, Galati S, Milano F, Rossi C, Buschini A Antiproliferative activity and chemoprotective effects towards DNA oxidative damage of fresh and cooked Brassicaceae..  British J Nutr. 2012;107:1324-32.

-Baruffini, E., Serafini, F., Ferrero, I. and Lodi, T. Overexpression of DNA Polymerase Zeta Reduces the Mitochondrial Mutability Caused by Pathological Mutations in DNA Polymerase Gamma in Yeast. PLOS One 2012; 7 e34322.

-Ghezzi, D., Baruffini, E., Haack, T.B., Invernizzi, F., Melchionda, L., Dallabona, C., Strom, T.M., Parini, R., Burlina, A.B., Meitinger, T., Prokisch, H., Ferrero, I., Zeviani, M. Mutations of the Mitochondrial-tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis. Am J Hum Genet 2012; 90 1079-87.]

-Rizzetto, L., Zanni, E., Uccelletti, D., Ferrero, I., Goffrini, P. (2012). Extension of Chronological Lifespan by Hexokinase Mutation in Kluyveromyces lactis Involves Increased Level of the Mitochondrial Chaperonin Hsp60. J Aging Res 2012 Epub 2012 May 17

-  Baruffini E, Horvath R, Dallabona C, Czermin B, Lamantea E, Bindoff L, Invernizzi F, Ferrero I, Zeviani M, Lodi T. Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model. Mitochondrion. 2011;11:182-190.

-  Turroni F, Bottacini F, Foroni E, Mulder I, Kim JH, Zomer A, Sánchez B, Bidossi A, Ferrarini A, Giubellini V, Delledonne M, Henrissat B, Coutinho P, Oggioni M, Fitzgerald GF, Mills D, Margolles A, Kelly D, van Sinderen D, Ventura M.  Genome analysis of Bifidobacterium bifidum PRL2010 reveals metabolic pathways for host-derived glycan foraging. Proc Natl Acad Sci U S A 2011;107:19514-9.

-  Dallabona C, Marsano RM, Arzuffi P, Ghezzi D, Mancini P, Zeviani M, Ferrero I, Donnini C. Sym1, the yeast ortholog of the MPV17 human disease protein, is a stress−induced bioenergetic and morphogenetic mitochondrial modulator. Human Molecular Genetics 2010;19:1098−1107.

-  Tuppen HA, Fehmi J, Czermin B, Goffrini P, Meloni F, Ferrero I, He L, Blakely EL, McFarland R, Horvath R, Turnbull DM, Taylor RW. Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation. Mol Genet Metab. 2010; 100:345-348.

- Gerra G, Zaimovic A, Castaldini L, Garofano L, Manfredini M, Somaini L, Leonardi C, Gerra ML, Donnini C.  Relevance of perceived childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility. Am J Med Genet B Neuropsychiatr Genet. 2010;153:715-722.

-  Stewart JD, Horvath R, Baruffini E, Ferrero I, Bulst S, Watkins PB, Fontana RJ, Day CP, Chinnery, PF. Polymerase gamma Gene POLG determines the risk of sodium valproate-induced liver toxicity. Hepatology 2010;52:1791-1796.

-  Degola F, Berni E, Spotti E, Ferrero I, Restivo FM. Facing the problem of "false positives": re-assessment and improvement of a multiplex RT-PCR procedure for the diagnosis of A. flavus mycotoxin producers. Int J Food Microbiol. 2009;129:300-5.

-  Goffrini P, Ercolino T, Panizza E, Giache V, Cavone L, Chiarugi A, Dima V, Ferrero I, Mannelli M. Functional study in a yeast model of a novel succinate-dehydrogenase subunit B gene germline missense mutation (C191Y) diagnosed in a patient affected by a glomus tumor. Human Molecular Genetics 2009;18:1860-1868.

- Buschini A, Pinelli S, Pellacani C, Giordani F, Ferrari MB, Bisceglie F, Giannetto M, Pelosi G, Tarasconi P. Synthesis, characterization and deepening in the comprehension of the biological action mechanisms of a new nickel complex with antiproliferative activity. J Inorg Biochem. 2009;103:666-77.

-  Ghezzi D, Goffrini P, Uziel G, Horvath R, Klopstock T, Lochmuller H, D'Adamo P, Gasparini P, Strom TM, Prokisch H, Invernizzi F, Ferrero I, Zeviani M. SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Nature Genetics 2009;41:654-656.