- Study of the molecular mechanisms of mitochondrial functions in yeast and extension of the model to the study of human mitochondrial disorders. Expression and functional analysis in S. cerevisiae of allegedly 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 action mechanisms 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.

-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.

-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).

-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 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.

• Molecular cloning and site directed mutagenesis

• Gene expression analysis

• Determination of ROS and mitochondrial membrane potential

• Drug discovery in yeast

• Mitochondrial DNA mutability, mtDNA content and mitochondrial protein synthesis

• Recombinant protein expression

• Western Blot, Immunoprecipitation

• Mutagenicity testing: Single cell gel electrophoresis (Comet assay); Cytokinesis-block micronucleus assay; Bacterial reverse mutation test (Ames test); Gene conversion, mitotic crossing over and reversion assays in S. cerevisiae

• General toxicity: MTT and MTS proliferation assay; Luminescent cell viability assay; Ethidium bromide/Hoechst33342 cell viability assay

• Global DNA methylation test

A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension.

Chin HL, Goh DL, Wang FS, Tay SKH, Heng CK, Donnini C, Baruffini E, Pines O.

J Mol Med (Berl). 2019 Nov;97(11):1557-1566. doi: 10.1007/s00109-019-01834-5.

Antiaflatoxigenic Thiosemicarbazones as Crop-Protective Agents: A Cytotoxic and Genotoxic Study.

Bartoli J, Montalbano S, Spadola G, Rogolino D, Pelosi G, Bisceglie F,  Restivo FM, Degola F, Serra O, Buschini A, Feretti D, Zani C, Carcelli M.

J Agric Food Chem. 2019 Oct 2;67(39):10947-10953. doi: 10.1021/acs.jafc.9b01814.

Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease.

Oláhová M, Ceccatelli Berti C, Collier JJ, Alston CL, Jameson E, Jones SA, Edwards N, He L, Chinnery PF, Horvath R, Goffrini P, Taylor RW, Sayer JA.

Hum Mol Genet. 2019 Aug 22. pii: ddz202. doi: 10.1093/hmg/ddz202.

Sabotage at the Powerhouse? Unraveling the Molecular Target of 2-Isopropylbenzaldehyde Thiosemicarbazone, a Specific Inhibitor of Aflatoxin Biosynthesis and Sclerotia Development in Aspergillus flavus, Using Yeast as a Model System.

Dallabona C, Pioli M, Spadola G, Orsoni N, Bisceglie F, Lodi T, Pelosi G, Restivo FM, Degola F.

Molecules. 2019 Aug 16;24(16). pii: E2971. doi: 10.3390/molecules24162971.

Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy.

Verrigni D, Di Nottia M, Ardissone A, Baruffini E, Nasca A, Legati A, Bellacchio E, Fagiolari G, Martinelli D, Fusco L, Battaglia D, Trani G, Versienti G, Marchet S, Torraco A, Rizza T, Verardo M, D'Amico A, Diodato D, Moroni I, Lamperti C, Petrini S, Moggio M, Goffrini P, Ghezzi D, Carrozzo R, Bertini E.

Hum Mutat. 2019 May;40(5):601-618. doi: 10.1002/humu.23729. Epub 2019 Mar 9.

Aspergillus flavus as a Model System to Test the Biological Activity of Botanicals: An Example on Citrullus colocynthis L. Schrad. Organic Extracts.

Degola F, Marzouk B, Gori A, Brunetti C, Dramis L, Gelati S, Buschini A, Restivo FM.

Toxins (Basel). 2019 May 22;11(5). pii: E286. doi: 10.3390/toxins11050286.

Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome.

Sharkia R, Wierenga KJ, Kessel A, Azem A, Bertini E, Carrozzo R, Torraco A, Goffrini P, Ceccatelli Berti C, McCormick ME, Plecko B, Klein A, Abela L, Hengel H, Schöls L, Shalev S, Khayat M, Mahajnah M, Spiegel R.

J Inherit Metab Dis. 2019 Mar;42(2):264-275.

Deciphering OPA1 mutations pathogenicity by combined analysis of human, mouse and yeast cell models.

Del Dotto V, Fogazza M, Musiani F, Maresca A, Aleo SJ, Caporali L, La Morgia C, Nolli C, Lodi T, Goffrini P, Chan D, Carelli V, Rugolo M, Baruffini E, Zanna C.

Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3496-3514. doi: 10.1016/j.bbadis.2018.08.004.

Sideroblastic anemia with myopathy secondary to novel, pathogenic missense variants in the YARS2 gene.

Smith F, Hopton S, Dallabona C, Gilberti M, Falkous G, Norwood F, Donnini C, Gorman GS, Clark B, Taylor RW, Kulasekararaj AG.

Haematologica. 2018 Dec;103(12):e564-e566. doi: 10.3324/haematol.2018.194464.

Pathogenic variants in glutamyl-tRNA^Gln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Friederich MW, Timal S, Powell CA, Dallabona C, Kurolap A, Palacios-Zambrano S, Bratkovic D, Derks TGJ, Bick D, Bouman K, Chatfield KC, Damouny-Naoum N, Dishop MK, Falik-Zaccai TC, Fares F, Fedida A, Ferrero I, Gallagher RC, Garesse R, Gilberti M, González C, Gowan K, Habib C, Halligan RK, Kalfon L, Knight K, Lefeber D, Mamblona L, Mandel H, Mory A, Ottoson J, Paperna T, Pruijn GJM, Rebelo-Guiomar PF, Saada A, Sainz B Jr, Salvemini H, Schoots MH, Smeitink JA, Szukszto MJ, Ter Horst HJ, van den Brandt F, van Spronsen FJ, Veltman JA, Wartchow E, Wintjes LT, Zohar Y, Fernández-Moreno MA, Baris HN, Donnini C, Minczuk M, Rodenburg RJ, Van Hove JLK.

Nat Commun. 2018 Oct 3;9(1):4065. doi: 10.1038/s41467-018-06250-w.

Pathological alleles of MPV17 modeled in the yeast Saccharomyces cerevisiae orthologous gene SYM1 reveal their inability to take part in a high molecular weight complex.

Gilberti M, Baruffini E, Donnini C, Dallabona C.

PLoS One. 2018 Oct 1;13(10):e0205014. doi: 10.1371/journal.pone.0205014. eCollection 2018.

Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.

Gerra MC, Jayanthi S, Manfredini M, Walther D, Schroeder J, Phillips KA, Cadet JL, Donnini C.

Transl Psychiatry. 2018 Jan 22;8(1):23. doi: 10.1038/s41398-017-0087-1.