CNR - National Research Council, Italy
IBPM - Institute of Biology and Molecular Pathology
Nucleic Acids Laboratory
c/o Dept. Biology and Biotechnology, University «La Sapienza», Rome (Italy)
- In short. My main interest centres on the relevance of chromosome architecture to genome functions. It's what I like to call functional morphogenomics.
- Bread and butter. Following my initial training in molecular biology and electron microscopy of nucleic acids I have been involved in research on the supramolecular organisation of the eukaryotic genome. This line is exemplified by studies on the relationship between replicative processes and the DNA loop organization of the genome, as well as by investigations on the role of this peculiar structural level of chromatin in determining genome complexity through the strict association of specific DNA regions (commonly known as MAR, SAR) to the non-histone protein framework of the nucleus (nuclear matrix, nucleoskeleton) and of the chromosomes (scaffold).
Our observations stress (a) the nuceoskeletal association of replicative intermediates and activities; (b) the close relationship between units of replication and nucleoskeleton-bound DNA loops; (c) the topological independence of each negatively supercoiled DNA loop domain from its neighbouring ones; (d) the possible significance of ‘origin of replication’ of MARs; (e) the immediate relevance of loop size variations to chromosome morphology ; (f) the key role of endogenous topoisomerase activities in shaping the looped architecture of the genome; and (g) the dependency of the binding specificity between MARs and the nucleoskeleton not only on the primary structure of the DNA, but also on the genomic context surrounding MARs in vivo.
- Side effects. Banking on the experience gained through the work on the eukaryotic genome, I got involved in studies on the organisation of the bacterial genome. The identification of global and local determinants of genome architecture is central also in microorganisms. As compared to its eukaryotic counterpart, the bacterial nucleoid offers the added advantage of a reduced biochemical and morphological complexity. Our investigations on global determinants indicate that histone-like proteins, surmised of being key elements in organizing the bacterial chromatin and well known as global regulators of bacterial gene expression, play an ancillary role in defining and maintaining the structural constrains which account for the topological integrity of the DNA loop domains in the bacterial nucleoid. As for local determinants, more recently I focused on the role of sequence-mediated DNA curvature (intrinsic bending) in the activity of virulence promoters in human enteropathogenic bacteria, like Shigella and E.coli EIEC. In these microorganisms the invasivity functions are modulated antagonistically by two histone-like proteins (H-NS and FIS), and the activation of the primary regulator (the virF gene) is triggered by the transit of the bacteria from the outer environment to the intestinal, warmer, milieu of the host. Our results show (a) that, among human enteropathogenic bacteria, the involvement of histone-like proteins in the transcriptional modulation of virulence gene networks is a common regulative strategy; (b) that the activation of the primary regulator is directly related to the changes in DNA bending its promoter undergoes with changing temperature; and (c) that an exquisitely structural feature of DNA, like intrinsic curvature, can act as a (thermo)sensor able to regulate gene expression in response to changing environmental conditions. As for the overall transcriptional significance of DNA curvature, our observations have allowed us to show that the in vitro activity of a bacterial promoter is maximized only within a narrow range of promoter curvature.
- House special. Part of my time is devoted to coordinating the activity of the IBPM's Molecular Microscopy Unit which focuses on electron microscopy and atomic force microscopy of nucleic acids and chromatin.
- Keywords (structures, processes, techniques). 3D genome architecture, supramolecular genome structure, chromatin-loops / morphogenomics / cell nucleus and chromosome structure / nuclear matrix, nucleoskeleton, nuclear lamina, chromosome scaffold / bacterial nucleoid structure / DNA, chromatin and nucleoproteins structure and organisation / DNA topology, topoisomerases / DNA intrinsic curvature, bending / epigenetics regulation, DNA replication, transcription, gene expression / electron microscopy, TEM, atomic force microscopy, AFM, SFM.
- Born in Rome (Italy), October 28th, 1953.
- Nationality: Italian
- High school: Schweizerschule, Rome, and Liceo scientifico A.Righi, Rome.
- 1980: Laurea in Biological Sciences at the University of Rome (Italy). Thesis project: Electron microscope analysis of DNA replication in Carassius auratus (supervisor: Prof. M.Buongiorno-Nardelli).
- 1980-1981: Research activity at the Institute of Histology and Embryology, Univ. Rome. Research project: Functional significance of the supercoiled loop organization of the eukaryotic genome (supervisor: Prof. M.Buongiorno-Nardelli).
- 1982-1983: Research fellow of the Istituto Pasteur-Fondazione Cenci Bolognetti (Univ.Rome) at the Zoologisches Institut (Abt. Zell- und Entwicklungsbiologie), Univ. Bern (Switzerland). Research project: Organisation of globin genes in Xenopus laevis (supervisor: Prof. R. Weber).
- 1983: Research assistant at the Zoologisches Institut (Abt. Zell- und Entwicklungsbiologie), Univ. Bern (Switzerland). Research project/supervisor: as above.
- Since 1984: staff scientist of the Italian National Research Council (CNR.) at the Centro Acidi Nucleici, Rome (currently: Laboratorio Acidi Nucleici of the IBPM, Institute of Molecular Biology and Pathology, CNR Rome). Research activity: see description.
- Summer 1995: visiting scientist (supported by a fellowship of the Consorzio Italiano Biotecnologie) in the laboratory of Prof. C. Bustamante at the Institute of Molecular Biology, Univ. Oregon, Eugene (Oregon, USA), specializing in atomic force microscopy of nucleic acids and chromatin.
- Since 2008: expert participating in the evaluation of EC FP6 and H2020 projects
Bibliometrics / Research ID:
List of publications (with links to Pubmed if available):
- Di Felice F, Micheli G, Camilloni G (2019). Restriction enzymes and their use in molecular biology: An overview. J Biosci 44:38
- Leuzzi A, Grossi M, Di Martino ML, Pasqua M, Micheli G, Colonna B, Prosseda G (2017). Role of the SRRz/Rz1 lambdoid lysis cassette in the pathoadaptive evolution of Shigella. Int. J. Med. Microbiol. 307:268–275
- Bolondi A, Caldarelli F, Di Felice F, Durano D, Germani G, Michetti M, Tramutolo A, Micheli G, Camilloni G (2017). What is a Gene? A Two Sided View. Evol. Biol. 44:1-4
- Durano D, Lukacs A, Di Felice F, Micheli G, Camilloni G (2017). A novel role for Nhp6 proteins in histone gene regulation in Saccharomyces cerevisiae. Int J Biochem Cell Biol. 83:76-83
- Di Martino ML, Falconi M, Micheli G, Colonna B, Prosseda G (2016). The Multifaceted Activity of the VirF Regulatory Protein in the Shigella Lifestyle. Front. Mol. Biosci. 3:61
- Leuzzi A, Di Martino ML , Campilongo R, Falconi M, Barbagallo M, Marcocci L, Pietrangeli P, Casalino M, Grossi M, Micheli G, Colonna B, Prosseda G. (2015). Multifactor Regulation of the MdtJI Polyamine Transporter in Shigella. PLoS ONE 10:e0136744
- Campilongo R, Di Martino ML, Marcocci L, Pietrangeli P, Leuzzi A, Grossi M, Casalino M, Nicoletti M, Micheli G, Colonna B, Prosseda G. (2014). Molecular and functional profiling of the polyamine content in enteroinvasive E. coli: looking into the gap between commensal E. coli and harmful Shigella. PLos ONE 9:e106589
- Di Martino ML, Campilongo R, Casalino M, Micheli G, Colonna B, Prosseda G. (2013). Polyamines: Emerging players in bacteria-host interactions. Int J Med Microbiol. 303:484-491
- Prosseda G, Di Martino ML, Campilongo R, Fioravanti R, Micheli G, Casalino M, Colonna B. (2012). Shedding of genes that interfere with the pathogenic lifestyle: the Shigella model. Res Microbiol. 163:399-406
- Prosseda G., Mazzola A., Di Martino M.L., Tielker D., Micheli G., Colonna B. (2010). A temperature-induced narrow DNA curvature range sustains the maximum activity of a bacterial promoter in vitro. Biochemistry 49:2778-2785
- Irene C., Maciariello C., Micheli G., Theis J.F., Newlon C.S., Fabiani L. (2007). DNA elements modulating the KARS12 chromosomal replicator in Kluyveromyces lactis. Mol Genet Genomics 277:287-299
- Panelli S., Damiani G., Espen L, Micheli G., Sgaramella V. (2006). Towards the analysis of the genomes of single cells: further characterisation of the multiple displacement amplification. Gene 372:1-7
- Prosseda G., Falconi M., Giangrossi M., Gualerzi C.O., Micheli G., Colonna B. (2004). The virF promoter in Shigella: more than just a curved DNA stretch.2004. Mol. Microbiol. 51:523-537
- Prosseda G., Falconi M., Nicoletti M., Casalino M., Micheli G., Colonna B. (2002). Histone like proteins and the Shigella invasivity regulon. Res. Microbiol. 153:461-468
- Brunetti R.,Prosseda G., Beghetto E., Colonna B., Micheli G. (2001). The looped domain organization of the nucleoid in histone-like protein defective Escherichia coli strains. Biochimie 83:873-82
- Falconi M., Colonna B., Prosseda G., Micheli G., Gualerzi C.O. (1998). Thermoregulation of Shigella and Escherichia coli EIEC pathogenicity. A temperature-dependent structural transition od DNA modulates accessibility of virF promoter to transcriptional repressor H-NS. EMBO J. 17:7033-7043
- Prosseda G., Fradiani P.A., Di Lorenzo M., Falconi M., Micheli G., Casalino M., Nicoletti M., Colonna B. (1998). A role for H-NS in the regulation of the virF gene of Shigella and enteroinvasive Escherichia coli. Res. Microbiol. 149:15-25
- Ghelardini P, Liebart J.C., Di Zenzo G., Micheli G., D'Ari R., Paolozzi L. (1994). A novel illegitimate recombination event: precise excision and reintegration with the Mu gem mutant prophage. Mol. Microbiol. 13:709-718
- Steinkühler C, Carrì MT, Micheli G, Knoepfel L, Weser U, Rotilio G. (1994). Copper-dependent metabolism of Cu, Zn-superoxide dismutase in human K562 cells. Lack of specific transcriptional activation and accumulation of a partially inactivated enzyme. Biochemical Journal 302 (Pt 3):687-694
- Dente L., Cesareni G., Micheli G., Felici F., Folgori A., Luzzago A., Monaci P., Nicosia A., Delmastro P. (1994). Monoclonal antibodies that recognise filamentous phage: tools for phage display technology. Gene 148:7-13
- Carrì MT, Steinküler C, Micheli G, Rotilio G. (1994). Study on the regulation of Cu, Zn SOD in response to stress by copper. In: Frontiers of Reactive Oxygen Species in Biology and Medicine (Asada K, Yoshikawa T. eds), p.291-292, Elsevier Science B.V.
- Micheli G., Ciofi Luzzatto A.R., Carrì M.T., de Capoa A., Peliccia F. (1993). Chromosome length and DNA loop size dur ing early embryonic development of Xenopus laevis. Chromosoma 102:478-483
- Colonna B., Bernardini M.L., Micheli G., Maimone F., Nicoletti M., Casalino M. (1989). Antibiotic resistance transposons on a virulence plasmid from Salmonella wien. J. Chemother.1, 313-314.
- Colonna B., Bernardini M.L., Micheli G., Maimone F., Nicoletti M., Casalino M. (1988). The Salmonella wien virulence plasmid pZM3 carries Tn1935, a multiresistance transposon containing a composite IS1936-kanamycin resistance element. Plasmid 20:221-231.
- Amaldi F, Bertolini B, Carrì MT, Hassan G, Micheli G. (1987) In ricordo di Mario buongiorno-nardelli 1937–1983. Italian Journal of Zoology (formerly: Bollettino di Zoologia) 54:91-93
- Carrì M.T., Micheli G., Graziano E., Pace T., Buongiorno-Nardelli M. (1986). The relationship between chromosomal origins of replication and the nuclear matrix during the cell cycle. Exp. Cell Res. 164:426-436.
- Brunori M., Condò S., Bellelli A., Giardina B., Micheli G. (1985). Tadpole Xenopus laevis hemoglobin. Correlation between stucture and functional properties. J. Mol. Biol. 181:327-329.
- Guardiola J, Grimaldi G, Costantino P, Micheli G, Cervone F (1982). Loss of Nitrofuran Resistance in Fusarium oxysporum is Correlated with Loss of a 46.7 kb Circular DNA Molecule. Microbiology (formerly: Journal of General Microbiology) 128:2235-2242
- Buongiorno-Nardelli M., Micheli G., Carrì M.T., Marilley M. (1982). A relationship between replicon size and supercoiled loop domains in the eukaryotic genome. Nature 298:100-102.
- Micheli G., Baldari C.T., Carrì M.T., Di Cello G., Buongiorno-Nardelli M. (1982). An electron microscope study of chromosomal DNA replication in different eukaryotic systems. Exp. Cell Res. 137:127-140.
- Costantino P., Mauro M.L., Micheli G., Risuleo G., Hooykaas P.J.J., Schilperoort R. (1981). Fingerprinting and sequence homology of plasmids from different virulent strains of Agrobacterium rhizogenes. Plasmid 5:170-182.
- Buongiorno-Nardelli M, MicheliG, Amaldi F, Baldari CT, Bozzoni I (1980). Electron microscopic analysis of DNA replication in eukaryotes. Italian Journal of Zoology (formerly: Bollettino di Zoologia) 47:253-261
- Mauro M.L., Micheli G. (1979). DNA reassociation kinetics in diploid and phylogenetically tetraploid cyprinidae. J. Exp. Zool. 208:407-415.
- Dr. Gioacchino Micheli
Ist.Biologia e Patologia Molecolari, Lab.Acidi Nucleici
c/o Dip.Biologia e Biotecnologie, Ist.Fisiologia Generale, Univ. «La Sapienza»
P.le A.Moro, 5 - 00185 ROMA (Italy)
- Tel: (+39) 0649912246
- Fax: (+39) 0649912500
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Last update: January 29th, 2020.
© 2006-2020 Gioacchino Micheli