Guido Grandi

Docente a contratto: Dipartimento di Biologia Cellulare, Computazionale e Integrata - CIBIO

Docente a contratto: Centro Interdipartimentale di Scienze Mediche - CISMED

Via S. Maria Maddalena, 1 - 38122 Trento

tel. 0461 283495

guido.grandi[at]unitn [dot] it

Competenze:

Analisi funzionale

Resistenza agli antibiotici

	Formazione
	Place/date of birth: Milan, Italy - 29 November 1952 Education: Graduation in Biological Sciences (University of Rome, Italy - 21.06.1975), 110/110 “cum Laude”. Dissertation: “R factors and bacterial antibiotic resistance”
	Carriera accademica ed attività didattica
	“Post laurea” working experiences 1975 - 1976 Visiting scientist at Bristol University - UK (Sept.1975 - March 1976). 1976 – 1977 Military service, Lieutenant Italian Air Force (April 1976 - August 1977) 1977 - 1981 Microbiology Department Farmitalia - Carlo Erba, Milan, Italy. 1978 - 1979 Visiting scientist at the Genetics Institute, Pavia University, Italy. 1979 - 1981 Visiting scientist at the Public Health Research Institute, New York, NY, USA. 1981 - 1987 Head of Genetic Engineering, Assoreni, Milan, Italy. 1987 – 1995 Director of Biotechnology Research, EniRicerche, Rome/Milan (Italy) with the responsibility of two Biotechnology Centers, one located in Milan and the other in Monterotondo (Rome), counting approximately 100 employees in total. 1995 - 2002 Director, Molecular Biology Department, Chiron Vaccines, Siena, Italy. 2002 – 2008 Vice President, Head Biochemistry and Molecular Biology Department, Site Manager of the Siena Research Center, Member of the Board of Directors, Chiron Vaccines, Siena, Italy. 2008- 2014 Senior Project Leader, Novartis Vaccines and Diagnostics, Member of Board of Directors of Novartis Siena and Rosia Sites. 2006 Director of the Life Sciences Department of the CNR, Rome, Italy - In 2006, Dr Grandi was nominated Director of the Life Sciences Department of the National Research Council (CNR), a prestigious position involving the coordination and management of all Life Science projects carried out in the different CNR National Institutes. Dr Grandi accepted the position temporarily at no remuneration to keep his position in Novartis, pending approval by the CNR Board of Directors of specific conditions discussed and agreed upon with the President of CNR before applying for the position. Since the approval was delayed due to the change of the Italian Government, Dr Grandi resigned from CNR in October 2006. 2010–2014 Appointed Professor in Microbial Biotechnology, Immunology and Vaccinology at Trento University, Trento Italy 2015 - present Full Professor of Micorbiology and Clinical Microbbiology, Trento University, Trento, Italy Patents Dr Grandi is inventor/co-inventor of 99 patent families that have generated 428 patents granted worldwide in different countries. Several other patent applications are under evaluation by International Patent Authorities. Publications Edited Books 1. Genomics, Proteomics and Vaccines (2004). G. Grandi (ed.) John Wiley & Sons, Ltd, West Sussex, UK. 2. In Vitro Transcription and Translation (2006). G. Grandi (ed.) Humana Press, Totowa, NJ. Book chapters 1. R. Grifantini and G. Grandi (2009). Chlamydia trachomatis vaccines. In “New Generation Vaccines” Fourth Edition, Marcel Dekker, Inc. 2. G. Grandi (2006) Genomics and proteomics in reverse vaccinology. In “Microbial Proteomics: Functional Biology of Whole Organisms”. I. Humphery-Smith and M. Hecker (eds.) John Wiley & Sons, Ltd., Hoboken, NJ. In press. 3. N. Norais, I. Garaguso, G. Ferrari and G. Grandi (2007). In vitro transcription and translation coupled to two-dimensional electrophoresis for bacterial proteome analysis. In “In vitro transcription and translation, Methods in Molecular Biology Series” G. Grandi (ed.) Humana Press Inc., Totowa, NJ, Vol. 375, 183-209. 4. G. Grandi. Reverse vaccinology: A Critical Analysis. In “Encyclopedia of Genomics, Proteomics and Bioinformatics” (2007). L.B. Jorde, P.F.R. Little, M.J. Dunn and S. Subramaniam (eds.). John Wiley & Sons, Ltd., West Sussex, UK. 5. R. Rappuoli, V. Masignani, G. Grandi and J.L. Telford (2004). A genomic approach to Vaccine Development. In “Microbial Genomes” C.M. Fraser, T.D. Read and K.E. Nelson (eds.) Humana Press Inc., Totowa, NJ, 505-516. 6. J.L. Telford, I. Margarit y Ros, D. Maione, V. Masignani, Hervé Tettelin, G. Bensi and G. Grandi (2004). Vaccines against Pathogenic streptococci. In “Genomics, Proteomics and Vaccines” G. Grandi (ed.) John Wiley & Sons, Ltd., West Sussex, UK, 205-222. 7. G. Ratti, O. Finco and G. Grandi. Searching the chlamydia genomes for new vaccine candidates. In “Genomics, Proteomics and Vaccines” G. Grandi (eds) John Wiley & Sons, Ltd., West Sussex, UK, 245-266. 8. N. Norais, R. Nogarotto, E.T. Iacobini, I. Garaguso, R. Grifantini, G. Galli and G. Grandi (2003). Protein identification from 2-D gels using in vitro transcription translation products. In “Handbook of Proteomic Methods” P. Michael Conn (ed.) Humana Press Inc., Totowa, NJ, 17-28. 9. G. Grandi (2003). Antibacterial vaccine discovery in the genomic area. In “Recent Advances in Marine Biotechnology” F. Fingermann and R. Nagabhushanam (eds.) Science Publishers, Inc.. Enfield, NH, 1-12. 10. R. Grifantini, E. Bartolini, A. Muzzi, M. Draghi, E. Frigimelica, J. Berger, F. Randazzo and G. Grandi (2002). Gene expression profile in Neisseria Meningitidis and Neisseria lactamica upon host-cell contact: from basic research to vaccine development. In “Microarrays, Immune Response, and Vaccines” L. Aujame, N. Burdin, B. Dodet and M. Vicari (eds.) Ann. N.Y. Acad. Sci. 975, 202-216. 11. J.L. Telford, M. Pizza, G. Grandi and R. Rappuoli (2002). Reverse vaccinology: from genome to vaccine. In “Methods in Microbiology” B. Wren and N. Dorrel (eds.) Academic Press, London, UK. Vol. 33, 257-270. 12. G. Grandi, M.G. Pizza, E. Scarlato and R. Rappuoli (2000). Development of new vaccines by protein engineering. In "Protein Engineering in Industrial Biotechnology" Lilia Alberghina (ed.) Harwood Academic Publishers, The Netherlands, 267-275. 13. G. Grandi, I. Margarit, F. Frigerio, R. Nogarotto, G. Carpani, R. Grifantini and G. Galli (2000). Stabilization of industrial enzymes by protein engineering. In "Protein Engineering in Industrial Biotechnology" Lilia Alberghina (ed.) Harwood Academic Publishers, The Netherlands, 147-157. 14. G. Grandi and G. Galli (1992). Metalloproteases and their role in Biotechnology. In "Metal Ions in Biological Systems. Volume 28: "Degradation of Environmental Pollutants by Microorganisms and Their Metalloenzymes" H. Sigel (ed.) Marcel Dekker, Inc., New York. 15. G. Grandi, M. Del Bue, B. Andrews, R. Timm, P. Cosmina, E. Franchi, G. Viale, G. and S. Toma (1988). Construction and use of expression vectors in B.subtilis. In "Physiological and Genetic Modulation of Product Formation" VCH (ed), 147-162 16. D. Dubnau, G. Grandi, R. Grandi, T.J. Gryczan, J. Hahn, Y. Kozlov, G.A. Shivakumar (1981). Regulation of plasmid-specified MLS resistance in B.subtilis by conformational alteration of RNA structure. In "Molecular Biology, Pathogenicity and Ecology of Bacterial Plasmids" Plenum Press N.Y. 17. V. Sgaramella, G. De Fazio, L. Ferretti, G. Grandi, M. Mottes and E. Palla (1981). Cloning of foreign genes in B.subtilis: nature of blocks of the expression of the E. coli hisG gene. In "Molecular Biology, Pathogenicity and Ecology of Bacterial Plasmids" Plenum Press, New York. 18. V. Sgaramella, U. Bertazzoni, G. Grandi, C. Morandi, M. Mottes, M.L. Molli and L.A. Zonta-Sgaramella (1978). Characterization and use as a vector of a bifunctional B.subtilis plasmid. In “Genetic Engineering” H.W. Boyer and S. Nicosia (eds.) Elsevier, 33 Research articles in peer-reviewed journals 1. F. Berti, E. Campisi, C. Toniolo, L. Morelli, S. Crotti, R. Rosini, M.R. Romano, V. Pinto, B. Brogioni, G. Torricelli, R. Janulczyk, G. Grandi and I. Margarit (2014). Structure of the type IX Group B Streptococcus capsular polysaccharide and its evolutionary relationship with types V and VII. J Biol Chem. Jul 2. pii: jbc.M114.567974. [Epub ahead of print] 2. M. Parri, L. Pietrovito, A. Grandi, S. Campagnoli, E. De Camilli, F. Bianchini, S. Marchiò, F. Bussolino, B. Jin, P. Sarmientos, G. Grandi, G. Viale, P. Pileri, P. Chiarugi and R. Grifantini (2014). Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer. Angiogenesis. Jun 6. [Epub ahead of print] 3. C. Faralla, M.M. Metruccio, M. De Chiara, R. Mu, K.A. Patras, A. Muzzi, G. Grandi, I. Margarit, K.S. Doran and R. Janulczyk (2014). Analysis of two-component systems in group B Streptococcus shows that RgfAC and the novel FspSR modulate virulence and bacterial fitness. MBio. 5(3):e00870-14. 4. M. Gallotta, G. Gancitano, G. Pietrocola, M. Mora, A. Pezzicoli, G. Tuscano, E. Chiarot, V. Nardi-Dei, A.R. Taddei, S. Rindi, P. Speziale, M. Soriani, G. Grandi, I. Margarit and G. Bensi (2014). SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion. Infect Immun. 82:2890-2901. 5. L. Popov, J. Kovalski, G. Grandi, F. Bagnoli and M.R. Amieva (2014). Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection. Front Immunol.5:41. 6. M.L. Kuhn, P. Prachi, G. Minasov, L. Shuvalova, J. Ruan, I. Dubrovska, J. Winsor, M. Giraldi, M. Biagini, S. Liberatori, S. Savino, F. Bagnoli, W.F. Anderson and G. Grandi* (2014). Structure and protective efficacy of the Staphylococcus aureus autocleaving protease EpiP. FASEB J. 28:1780-1793. 7. E. Bartolini, E. Ianni, E. Frigimelica, R. Petracca, G. Galli, F. Berlanda Scorza, N. Norais, D. Laera, F. Giusti, A. Pierleoni, M. Donati, R. Cevenini, O. Finco, G. Grandi* and R. Grifantini (2013). Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro. J Extracell Vesicles. 2: 20181. 8. C. Schluepen, E. Malito, A. Marongiu, M. Schirle, E. McWhinnie, P. Lo Surdo, M. Biancucci, F. Falugi, V. Nardi-Dei, S. Marchi, M.R. Fontana, B.Lombardi, M.G. De Falco, C.D. Rinaudo, G. Spraggon, M. Nissum, F. Bagnoli, G. Grandi, M.J. Bottomley and S. Liberatori (2013). Mining the bacterial unknown proteome: identification and characterization of a novel family of highly conserved protective antigens in Staphylococcus aureus. Biochem J. 455:273-284. 9. A. Nuccitelli, C.D. Rinaudo, B. Brogioni, R. Cozzi, M. Ferrer-Navarro, D. Yero, J.L. Telford, G. Grandi, X. Daura, M. Zacharias and D. Maione (2013). Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of group B streptococcus. PLoS Comput Biol. 9:e1003115. 10. E. Chiarot, C. Faralla, N. Chiappini, G. Tuscano, F. Falugi, G. Gambellini, A. Taddei, S. Capo, E. Cartocci, D. Veggi, A. Corrado, S. Mangiavacchi, S. Tavarini, M. Scarselli, R. Janulczyk, G. Grandi, I. Margarit and G. Bensi (2013).Targeted amino acid substitutions impair streptolysin O toxicity and group A Streptococcus virulence. MBio. 4:e00387-12. 11. P.R. Dormitzer, G. Grandi and R. Rappuoli (2012) Structural vaccinology starts to deliver. Nat Rev Microbiol. 10:807-813. 12. R. Cozzi, D. Prigozhin, R. Rosini, F. Abate, M.J. Bottomley, G. Grandi, J.L. Telford, C.D. Rinaudo, D. Maione and T. Alber (2012). Structural basis for group B streptococcus pilus 1 sortases C regulation and specificity. PLoS One. 7:e49048. 13. P. Mariotti, E. Malito, M. Biancucci, P. Lo Surdo, R.P. Mishra, V. Nardi-Dei, S. Savino, M. Nissum, G. Spraggon, G. Grandi, F. Bagnoli and M.J. Bottomley (2012). Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2. Biochem. J. 449:683-693. 14. F. Bagnoli, S. Bertholet and G. Grandi (2012). Inferring Reasons for the Failure of Staphylococcus aureus Vaccines in Clinical Trials. Front Cell Infect Microbiol. 2:16. 15. N. Chiappini, A. Seubert, J.L. Telford, G. Grandi, D. Serruto, I. Margarit and R. Janulczyk (2012). Streptococcus pyogenes SpyCEP influences host-pathogen interactions during infection in a murine air pouch model. PLoS One. 7:e40411. 16. R.P. Mishra, P. Mariotti, L. Fiaschi, S. Nosari, S. Maccari, S. Liberatori, M.R. Fontana, A. Pezzicoli, M.G. De Falco, F. Falugi, E. Altindis, D. Serruto, Grandi G, and F. Bagnoli (2012). Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice. J Infect Dis. 206:1041-1049. 17. Becherelli M, Manetti A.G., Buccato S., Viciani E., Ciucchi L., Mollica G., Grandi G., Margarit I (2012). The ancillary protein 1 of Streptococcus pyogenes FCT 1 pili mediates cell adhesion and biofilm formation through heterophilic as well as homophilic interactions. Mol. Microbiol. 83, 1035 -1047 18. Fabbrini M, Sammicheli C, Margarit I, Maione D, Grandi G, Giuliani MM, Mori E, Nuti S. (2012) A new flow-cytometry-based opsonophagocytosis assay for the rapid measurement of functional antibody levels against Group B Streptococcus. J Immunol Methods. 378:11-19. 19. G. Bensi, M. Mora, G. Tuscano, M. Biagini, E. Chiarot, M. Bombaci, S. Capo, F. Falugi, A.G. Manetti, P. Donato, E. Swennen, M. Gallotta, M. Garibaldi, V. Pinto, N. Chiappini, J.M. Musser, R. Janulczyk, M. Mariani, M. Scarselli, J.L. Telford, R. Grifantini, N. Norais, I. Margarit and G. Grandi (2012). Multi High-Throughput Approach for Highly Selective Identification of Vaccine Candidates: the Group A Streptococcus Case. Mol. Cell. Proteomics. 11:M111.015693. 20. Cozzi R, Nuccitelli A, D'Onofrio M, Necchi F, Rosini R, Zerbini F, Biagini M, Norais N, Beier C, Telford JL, Grandi G, Assfalg M, Zacharias M, Maione D, Rinaudo CD (2012). New insight into the role of glutamic acid of the E-Box motif in Group B Streptococcus pilus 2a assembly. FASEB J. 26:2008-2018. 21. C.L. Galeotti, E. Bove, A. Pezzicoli, R. Nogarotto, N. Norais, S. Pileri, B. Lelli, F. Falugi, S. Balloni, V. Tedde, E. Chiarot, M. Bombac, M. Soriani, L. Bracci, G. Grandi* and R. Grifantini (2012). Surface Interactome in Streptococcus pyogenes. Mol. Cell. Proteomics. 11:M111.015206. 22. F. Necchi, V. Nardi-Dei, M. Biagini, M. Assfalg, A. Nuccitelli, R. Cozzi, N. Norais, J.L.Telford, C.D. Rinaudo, G. Grandi and D. Maione (2011). Sortase A substrate specificity in GBS pilus 2a cell wall anchoring. PLoS One. 6:e25300. 23. R. Grifantini, M. Pagani, A. Pierleoni, A. Grandi, M Parri, S. Campagnoli, P. Pileri, D. Cattaneo, E. Canidio, A. Pontillo, E. De Camilli, A. Bresciani, F. Marinoni, E. Pedrazzoli, R. Nogarotto, S. Abrignani, G. Viale, P. Sarmientos and G. Grandi (2011). A novel polyclonal antibody library for expression profiling of poorly characterized, membrane and secreted human proteins. J. Proteomics. 75:532-547. 24. O. Finco, E. Frigimelica, F. Buricchi, R. Petracca, G. Galli, E. Faenzi, E. Meoni, A. Bonci, M. Agnusdei, F. Nardelli, E. Bartolini, M. Scarselli, E. Caproni, D. Laera, L. Zedda, D. Skibinski, S. Giovinazzi, R. Bastone, E. Ianni, R. Cevenini, G. Grandi*** and R. Grifantini (2011). Approach to discover T and B cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines. Proc. Natl. Acad. Sci. U S A. 108:9969-9974. 25. A. Nuccitelli, R. Cozzi, L.J. Gourlay, D. Donnarumma, F. Necchi, N. Norais, J.L. Telford. R. Rappuoli, M. Bolognesi, D. Maione, G. Grandi* and C.D. Rinaudo (2011). A structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections. Proc. Natl. Acad. Sci. U S A. 108:10278-10283. 26. R. Cozzi, E. Malito, A. Nuccitelli, M. D'Onofrio, M. Martinelli, I. Ferlenghi, G. Grandi, J.L. Telford, D. Maione and C.D. Rinaudo (2011). Structure analysis and site-directed mutagenesis of defined key residues and motives for pilus-related sortase C1 in group B Streptococcus. FASEB J. 25:1874-1886. 27. G. Grandi* (2010). Bacterial vaccine discovery: From "brute force" to high selectivity. Hum Vaccin. 6:7-10. 28. A.G. Manetti, T. Köller, M. Becherelli, S. Buccato, B. Kreikemeyer, A. Podbielski, G. Grandi* and I. Margarit I (2010). Environmental acidification drives S. pyogenes pilus expression and microcolony formation on epithelial cells in a FCT-dependent manner. PLoS One. 5:e13864. 29. G. Grandi* (2010). Bacterial surface proteins and vaccines. F1000 Biol Rep. 2. pii: 36. 30. A. Kabanova, I. Margarit, F. Berti, M.R. Romano, G. Grandi, G. Bensi, E. Chiarot, D. Proietti, E. Swennen, E. Cappelletti, P. Fontani, D. Casini, R. Adamo, V. Pinto, D. Skibinski, S. Capo, G. Buffi, M. Gallotta, W.J. Christ, A.S. Campbell, J. Pena, P.H. Seeberger, R. Rappuoli and P. Costantino (2010) Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate. Vaccine. 29:104-114. 31. M. Soriani, P. Petit, R. Grifantini, R. Petracca, G. Gancitano, E. Frigimelica, F. Nardelli, C. Garcia, S. Spinelli, G. Scarabelli, S. Fiorucci, R. Affentranger, M. Ferrer-Navarro, M. Zacharias, G. Colombo, L. Vuillard, X. Daura and G. Grandi* (2010). Exploiting antigenic diversity for vaccine design: the Chlamydia ArtJ paradigm. J. Biol. Chem. 285:30126-30138. 32. R. Janulczyk, V. Masignani, D. Maione, H. Tettelin, G. Grandi and J.L. Telford (2010). Simple sequence repeats and genome plasticity in Streptococcus agalactiae. J. Bacteriol. 192:3990-4000. 33. C. Zingaretti, F. Falugi, V. Nardi-Dei, G. Pietrocola, M. Mariani, S. Liberatori, M. Gallotta, M. Tontini, C. Tani, P. Speziale, G. Grandi* and I. Margarit I (2010). Streptococcus pyogenes SpyCEP: a chemokine-inactivating protease with unique structural and biochemical features. FASEB J. 24:2839-2848. 34. C.D. Rinaudo, R. Rosini, C.L. Galeotti, F. Berti, F. Necchi, V. Reguzzi, C. Ghezzo, J.L. Telford, G. Grandi and D. Maione (2010). Specific involvement of pilus type 2a in biofilm formation in group B Streptococcus.PLoS One. 5:e9216. 35. T. Köller, A.G. Manetti, B. Kreikemeyer, C. Lembke, I. Margarit, G. Grandi and A. Podbielski (2010). Typing of the pilus-protein-encoding FCT region and biofilm formation as novel parameters in epidemiological investigations of Streptococcus pyogenes isolates from various infection sites. J. Med. Microbiol. 59:442-452. 36. L.J. Gourlay, G. Colombo, M. Soriani, G. Grandi, X. Daura and M. Bolognesi (2009). Why is a protective antigen protective? Hum. Vaccin. 5:872-875. 37. M. Bombaci, R. Grifantini, M. Mora, V. Reguzzi, R. Petracca, E. Meoni, S. Balloni, C. Zingaretti, F. Falugi, A.G. Manetti, I. Margarit, J.M. Musser, F. Cardona, G. Orefici, G. Grandi* and G. Bensi (2009). Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens. PLoS One. 4:e6332. 38. E. Meoni, E. Faenzi, E. Frigimelica, L. Zedda, D. Skibinski, S. Giovinazzi, A. Bonci, R. Petracca, E. Bartolini, G. Galli, M. Agnusdei, F. Nardelli, F. Buricchi, N. Norais, I. Ferlenghi, M. Donati, R. Cevenini, O. Finco, G. Grandi* and R. Grifantini (2009). CT043, a protective antigen that induces a CD4+ Th1 response during Chlamydia trachomatis infection in mice and humans. Infect. Immun. 77:4168-4176. 39. I. Santi, D. Maione, C.L. Galeotti, G. Grandi, J.L. Telford and M. Soriani (2009). BibA induces opsonizing antibodies conferring in vivo protection against group B Streptococcus. J. Infect. Dis. 200:564-570. 40. I. Santi, R. Grifantini, S.M. Jiang, C. Brettoni, G. Grandi, M.R. Wessels and M. Soriani (2009). CsrRS regulates group B Streptococcus virulence gene expression in response to environmental pH: a new perspective on vaccine development. J. Bacteriol. 191:5387-5397. 41. L.J. Gourlay, I Santi, A. Pezzicoli, G. Grandi, M. Soriani and M. Bolognesi (2009).Group B streptococcus pullulanase crystal structures in the context of a novel strategy for vaccine development. J. Bacteriol. 191:3544-3552. 42. I. Margarit, S. Bonacci, G. Pietrocola, S. Rindi, C. Ghezzo, M. Bombaci, V. Nardi-Dei, R. Grifantini, P. Speziale and G. Grandi* (2009). Capturing host-pathogen interactions by protein microarrays: identification of novel streptococcal proteins binding to human fibronectin, fibrinogen, and C4BP. Faseb J. 23: 3100-3012. 43. F. Doro, S. Liberatori, M.J. Rodríguez-Ortega, C.D. Rinaudo, R. Rosini, M. Mora, M. Scarselli, E. Altindis, R. D'Aurizio, M. Stella, I. Margarit, D. Maione, J.L.Telford, N. Norais and G. Grandi* (2009). Surfome analysis as a fast track to vaccine discovery: Identification of a novel protective antigen for group B Streptococcus hyper-virulent strain COH1. Mol. Cell. Proteomics, 8: 1728-1737. 44. I. Margarit, C.D. Rinaudo, C.L. Galeotti, D. Maione, C. Ghezzo, E. Buttazzoni, R. Rosini, Y. Runci, M. Mora, S. Buccato, M. Pagani, E. Tresoldi, A. Berardi, R. Creti, C.J. Baker, J.L. Telford and G. Grandi* (2009). Preventing bacterial infections with pilus-based vaccines: the group B streptococcus paradigm. J. Infect. Dis. 199:108-115. 45. I. Santi, A. Pezzicoli, M. Bosello, F. Berti, M. Mariani, J.L. Telford, G. Grandi and M. Soriani (2008). Functional characterization of a newly identified group B streptococcus pullulanase eliciting antibodies able to prevent alpha-glucans degradation. PLoS ONE 3:e3787. 46. F. Falugi, C. Zingaretti, V. Pinto, M. Mariani, L. Amodeo, A.G.O. Manetti, S. Capo, J.M. Musser, G. Orefici, I. Margarit, J.L. Telford, G. Grandi* and M. Mora (2008). Sequence variation in Group A Streptococcus pili and association of pilus backbone types with Lancefield T-serotypes. J Infect Dis. 198:1834-1841 47. A. Pezzicoli, I. Santi, P. Lauer, R. Rosini, C.D. Rinaudo, G. Grandi and J.L. Telford and M. Soriani (2008). Pilus backbone contributes to group B Streptococcus paracellular translocation through epithelial cells. J. Infect. Dis. 198:890-898. 48. A.H. Nobbs, R. Rosini, C.D. Rinaudo, D. Maione, G. Grandi and J.L. Telford (2008). Sortase A utilizes an ancillary protein anchor for efficient cell wall anchoring of pili in Streptococcus agalactiae. Infect. Immun. 76:3550-3560. 49. E. Frigimelica, E. Bartolini, G. Galli, G. Grandi* and R. Grifantini (2008). Identification of 2 hypothetical genes involved in Neisseria meningitidis cathelicidin resistance. J Infect Dis. 197:1124-1132. 50. A.M. Edwards, A.G. Manetti, F. Falugi, C. Zingaretti, S. Capo, S. Buccato, G. Bensi, J.L. Telford, I. Margarit and G. Grandi* (2008). Scavenger receptor gp340 aggregates group A streptococci by binding pili. Mol Microbiol. 68:1378-1394. 51. P. Sumby, S. Zhang, A.R. Whitney, F. Falugi, G. Grandi, E.A. Graviss, F.R. Deleo and J.M. Musser (2008). A chemokine-degrading extracellular protease made by group a streptococcus alters pathogenesis by enhancing evasion of the innate immune response. Infect Immun. 76:978-985. 52. F. Berlanda Scorza, F. Doro, M.J. Rodríguez-Ortega, M. Stella, S. Liberatori, A.R. Taddei, L. Serino, D. Gomes Moriel, B. Nesta, M.R. Fontana, A. Spagnuolo, M.Pizza, N. Norais and G. Grandi* (2008). Proteomic characterization of outer membrane vesicles from the extraintestinal pathogenic Escherichia coli tolR IHE3034 mutant. Mol. Cell. Proteomics, 7: 473-485. 53. I. Gryllos, R. Grifantini, A. Colaprico, S. Jiang, E. Deforce, A. Hakansson, J.L. Telford, G. Grandi* and M.R. Wessels (2007). Mg(2+) signalling defines the group A streptococcal CsrRS (CovRS) regulon. Mol. Microbiol., 65: 671-683. 54. A.G.O. 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Tosi and G. Grandi* (1997). Engineering of peptide synthetases: key role of the thioesterase-like domain for efficient production of recombinant peptides. J. Biol. Chem., 272, 25304-25309. 108. M. de Bernard, B. Aricò, E. Papini, G. Grandi, R. Rizzuto, R. Rappuoli and C. Montecucco (1997). Helicobacter pylori toxin VacA induces vacuole formation from the cell cytosol. Mol.Microbiol., 26, 665-674. 109. M. Copass, G. Grandi* and R. Rappuoli (1997). Introduction of unmarked mutations in the Helicobacter pylori vacA gene with a sucrose sensitivity marker. Infection and Immunity, 65, 1949-1952. 110. P. Ruggiero, P. Bossù, G. Macchia, E. Del Grosso, V. Sabbatini, R. Bertini, A. Colagrande, C. Bizzarri, G. Maurizi, V. Di Cioccio, G. D'Andrea, A. Di Giulio, F. Frigerio, R. Grifantini, G. Grandi, A. Tagliabue, D. Boraschi (1997). Inhibitory activity of IL-1 antagonist depends on the balance between binding capacity for IL-1 receptor type 1 and IL-1 receptor type II. J. Immunol., 158, 3881-3887. 111. F. Frigerio, I. Margarit, R. Nogarotto, G. Grandi, G. Vriend, F. Hardy, O.R. Veltman, G. Venema and V.G. Eijsink (1997). Model building of a thermolysin-like protease by mutagenesis. Protein Eng. 10, 223-230. 112. R. Grifantini, C. Pratesi, G. Galli and G. Grandi* (1996). Topological mapping of the cysteine residues of N-carbamyl-D-amino-acid amidohydrolase and their role in enzymatic activity. J. Biol. Chem., 271, 9326-9331. 113. F. Frigerio, I. Margarit, R. Nogarotto, V. de Filippis and G. Grandi* (1996). Cumulative stabilizing effects of hydrophobic interactions on the surface of the neutral protease from Bacillus subtilis. Protein Engineering, 9, 439-445. 114. P. Pedroni, G.M. Mura, G. Galli, C. Pratesi, L. Serbolisca and G. Grandi* (1996). The hydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus: from basic research to possible future applications. J. Hydrogen Energy, 21, 853-858. 115. G.M. Mura, G. Galli, C. Pratesi, G. Frascotti, L. Serbolisca, P. Pedroni and G. Grandi* (1996). Photoinduced hydrogen production using titanium dioxide coupled to thermostable hydrogenases. J. Mar. Biotechnol., 4, 68-74. 116. G. M. Mura, P. Pedroni, C. Pratesi, G. Galli, L. Serbolisca and G. Grandi* (1996). The [Ni-Fe] hydrogenase from the thermophilic bacterium Acetomicrobium flavidum. Microbiology, 142, 829-836. 117. F. Rodriguez and G. Grandi* (1995). An operon encoding a novel Bacillus subtilis ABC-type transport system. Microbiology, 141, 1781-1784. 118. Tognoni, E. Franchi, C. Magistrelli, E. Colombo, P. Cosmina, and G. Grandi* (1995). A putative new peptide syntethase operon in B. subtilis. Microbiology, 141, 645-648. 119. P. Pedroni, A. Della Volpe, G. Galli, G.M. Mura, C. Pratesi and G. Grandi. (1995) Characterization of the locus encoding the [Ni-Fe] sulfhydrogenase from the archaeon Pyrococcus furiosus: evidence for a relationship to bacterial sulfite reductases. Microbiology, 141, 449-458. 120. D. Boraschi, P. Bossù, P. Ruggero, A. Tagliabue, R. Bertini, G. Macchia, C. Gasbarro, L. Pellegrini, G. Melillo, E. Ulisse, U. Visconti, C. Bizzarri, E, Del Grosso, A.R. Mackay, G. Frascotti, F. Frigerio, R. Grifantini and G. Grandi (1995) Mapping of receptor binding sites on IL-1 beta by reconstruction of IL-1ra-like domains. J. Immunol., 155, 4719-4725. 121. F. Hardy, G. Vriend, B. van de Vinne, F. Frigerio, G. Grandi, G. Venema and V.G.H.Eijsink (1994). The effect of engineering surface loops on the thermostability of B.subtilis neutral protease. Protein Engineering, 7, 425-430. 122. G. Galli, E. Rodriguez, P. Cosmina, C. Pratesi, R.Nogarotto, F. de Ferra and G. Grandi (1994). Characterization of surfactin synthetase multienzyme complex. Biochim. Biophys. Acta 1205, 19-28. 123. C. Scotti, S. Piatti, A. Cuzzoni, P. Perani, A. Tognoni, G. Grandi, A. Galizzi and A.M. Albertini (1993). A Bacillus subtilis large ORF coding for a polypeptide highly similar to polyketide synthases. Gene, 130, 65-71. 124. D. van Sinderen, G. Galli, P. Cosmina, F. de Ferra, S. Withoff, G. Venema and G. Grandi* (1993). Characterization of the srfA locus of B. subtilis: only the valine-activating domain of srfA is involved in the establishment of genetic competence. Molecular Microbiology, 8, 833-841. 125. P. Cosmina, F. Rodriguez, F. de Ferra, G. Grandi, M. Perego, G. Venema, D. van Sinderen (1993). Sequence and analysis of the genetic locus responsible for surfactin synthesis in Bacillus subtilis. Molecular Microbiology, 8, 821-831. 126. C. Magistrelli, E. Colombo, A. Tognoni and G. Grandi* (1992). Transfection of E. coli with λ DNA by electroporation. Microbiologica, 15, 397-398. 127. C. Ettori, P.G. Righetti, C. Chiesa, F. Frigerio, G. Galli, G. Grandi* (1992). Purification of recombinant human growth hormone by isoelectric focusing in a multicompartment electrolyzer with Immobiline membranes. J. Biotechnology, 25, 307-318. 128. Margarit, S. Campagnoli, F. Frigerio, G. Grandi, V. De Filippis and A. Fontana (1992). Cumulative Stabilizing Effects of Glycine to Alanine Substitutions in B. subtilis neutral protease. Protein Engineering, 5, 543-550. 129. D. Parente, F. de Ferra, G. Galli and G. Grandi* (1991). Prochymosin expression in B. subtilis. FEMS Microbiology Letters, 77, 243-249. 130. Velati Bellini, G. Galli, E. Fascetti, G. Frascotti, P. Branduzzi, G. Lucchese and G. Grandi. (1991) Production processes of recombinant IL-1beta from B. subtilis: comparison between intracellular and exocellular expression. J. Biotechnology, 18, 177-192. 131. Riboli, P. Pedroni, A. Cuzzoni, G. Grandi* and F. de Ferra (1991). Expression of Bordetella pertussis fimbrial (fim) genes in Bordetella bronchiseptica: fimX is expressed at a low level and vir-regulated. Microbial Pathogenesis, 10, 393-403. 132. S. Toma, S. Campagnoli, I. Margarit, R. Gianna, G. Grandi, M.Bolognesi, V.De Filippis and A.Fontana (1991). Grafting of a calcium binding loop of thermolysin to B. subtilis neutral protease. Biochemistry, 30, 97-106. 133. E. Franchi, F. Maisano, S. Astrua Testori, G. Galli, S. Toma, L. Parente, F. de Ferra and G. Grandi (1991). A new human growth hormone production process using a recombinant B. subtilis strain. J. Biotechnology, 18, 41-54. 134. G. Signor, C. Vita, A. Fontana, F. Frigerio, M. Bolognesi, S. Toma, R. Gianna, E. De Gregoriis and G. Grandi (1990). Structural features of neutral protease from B.subtilis deduced from model-building and limited proteolysis experiments. Eur.J.Biochemistry, 189, 221-227. 135. A. Cuzzoni, P. Pedroni, B. Riboli, G. Grandi and F. de Ferra (1990). Nucleotide sequence of the fim3 gene from Bordetella pertussis and homology to fim2 and fimX gene products. Nucleic Acids Res., 18, 1640. 136. G. Grandi, S. Toma, I. Margarit, S. Campagnoli, R. Gianna, A. Velati Bellini, M. Zamai and P. Carrera (1990). The Bacillus subtilis neutral protease: a model case for site-directed mutagenesis and protein engineering. Chemistry Today, 8, 9-13. 137. F. Maisano, D. Parente, A. Velati Bellini, P. Carrera, M. Zamai and G. Grandi (1989). A rapid and efficient method for the purification of synthetic oligonucleotides by High Performance Ion-Exchange Chromatography in volatile buffer. BioChromatography, 4, No 5, 279-281. 138. F. Maisano, S. Astrua Testori and G. Grandi* (1989). IMAC. Immobilized Metal-ion Affinity Chromatography of Human Growth Hormone. J. Chromatography, 472, 422-427. 139. S. Toma, S. Campagnoli, E. De Gregoriis, R. Gianna, I. Margarit, M. Zamai and G. Grandi* (1989). Effect of Glu144 and His228 substitutions on the catalytic activity and secretion of B.subtilis neutral protease. Protein Engineering, 2, 359-364. 140. F. de Ferra, P. Pedroni, B. Riboli, A. Cuzzoni and G. Grandi* (1988). B. pertussis pilin and pilin-like genes. Tokai J.Exp.Clin.Med., 13 (suppl.), 235-238. 141. A. Tognoni, P. Carrera, G. Galli, G. Lucchese, B. Camerini and G. Grandi* (1988). Cloning and nucleotide sequence of the isoamylase gene from a Pseudomonas sp. strain. J. Gen. Microbiol., 135, 37-45. 142. P. Pedroni, B. Riboli, F. de Ferra, G. Grandi, S. Toma, B. Aricò and R. Rappuoli (1988). Cloning of a novel pilin-like gene from B.pertussis: homology to the ST2 gene. Mol. Microbiol. 2, 539-543. 143. A. Velati Bellini, F. de Ferra and G. Grandi* (1988). A rapid and versatile site-directed method of mutagenesis on double stranded plasmid DNA. Gene, 69, 325-330. 144. M. Del Bue, P. Cosmina, E. Franchi, S. Toma and G. Grandi* (1987). Plasmid expression vectors for B.subtilis. Chimica Oggi, 3, 73-75. 145. S. Toma, M. Del Bue and G. Grandi* (1987). Neutral protease expression in B. subtilis. Chimica Oggi, 4, 71-72. 146. P. Carrera, G. Grandi and F. Maisano (1987). Plasmapping: an easy computer tool for display and storage of plasmid maps. Chimica Oggi, 11, 73-74. 147. S. Toma, M. Del Bue, A. Pirola and G. Grandi (1986). nprR1 and nprR2 regulatory regions for neutral protease expression in B.subtilis. J.Bacteriol., 167, 740-743. 148. G. Grandi, M. Del Bue, E. Palla, A. Mele, E. Colletti and S. Toma (1986). New plasmid expression vectors for B.subtilis. Plasmid, 16, 1-14. 149. G. Grandi, A. Mele, E. Colletti, S. Campagnoli and R. Nogarotto (1985) Effects of different promoters and terminators on the expression of pBR322 beta-lactamase in both E.coli and B. subtilis. J. Cellular Biochemistry, (9B). 150. J. Hahn, G. Grandi, T.J. Gryczan, D. Dubnau (1982). Translational attenuation of ErmC: a deletion analysis. Mol. Gen. Genet., 186, 204-216. 151. G. Grandi, M. Mottes and V. Sgaramella (1981). Specific pattern of instability of E.coli hisG gene cloned in B.subtilis via the S.aureus plasmid pCS194. Plasmid, 6, 99-111. 152. A. Fietta, G. Grandi, M. Malcovati, G. Valentini, V. Sgaramella and A. Siccardi (1981). R-factor mediated suppression of the galacto-sensitive phenotype of E.coli K12 galE mutants. Plasmid, 6, 78-85. 153. A. Docherty, G. Grandi, R. Grandi, T.J. Gryczan, A.G. Shivakumar and D. Dubnau (1981). Naturally occurring macrolide-lincosamide- streptogramin B resistance in B.licheniformis. J.Bacteriol., 145, 129-137. 154. T.J. Gryczan, G. Grandi, J. Hahn, R. Grandi and D. Dubnau (1980). Conformational alteration of mRNA structure and the posttranscriptional regulation of erythromycin-induced drug resistance. Nucl. Acids Res. 8, 6081-6097. 155. A.G. Shivakumar, J. Hahn, G. Grandi, Y. Kozlov and D. Dubnau (1980). Posttranscriptional regulation of an erjthromycin resistance protein specified by plasmid pE194. Proc. Natl. Acad. Sci. USA, 77, 3903-3907. 156. M. Mottes, G. Grandi, V. Sgaramella, U. Canosi, G. Morelli and G.A. Trautner (1979). Different specific activities of the Monomeric and Oligomeric forms of plasmid DNA in trasformation of B.subtilis and E.coli. Mol. Gen. Genet., 174, 281-286.
	Interessi di ricerca
	*Current research interests* At present, Dr Grandi is focusing his research interest in Structural Vaccinology, with the aim at designing antigens with broader and more potent protective activities (Rizzitelli et al., PNAS, 2011). He is also interested in elucidating and understanding the biological role of protein-protein interactions occurring at bacterial surfaces (Galeotti et al., Mol.Cell. Proteomics, 2012). As co-founder and Member of the Scientific Advisory Board of Externautics SpA Prof. Grandi is actively working on cancer biomarker discovery and the development of monoclonal antibodies in cancer therapy and diagnosis (Grifantini R., J. Proteom. (2011); Parri et al. Angiogenesis (2014)). Finally, Prof. G. Grandi has recently been assigned the prestigious ERC (European Research Council) advanced investigator grant. The five-year grant has officially started on June 1^st, 2014 and is focused on the use of Synthetic Biology for the development of a highly innovative vaccine platform for infectious diseases and cancer applications.
	Attività di ricerca
	Scientific Leadership profile *Bacillus subtilis biology and biotechnology* - Dr Grandi began his scientific career working on the genetics and molecular biology of Bacillus subtilis. During his post-doctoral period at the University of Pavia, he discovered that, differently from E. coli, plasmid transformation in B. subtilis occurs only in the presence of oligomers, a discovery that has been subsequently exploited by all scientists working in the field. Subsequently, after joining Dr. Dubnau’s laboratories at PHRI (New York, USA), he contributed to the elucidation of the mechanism of post-transcriptional regulation of erythromycin resistance, involving the formation of secondary structures at the 5’ end of the mRNA. This discovery paved the way to the understanding of the mechanism of post-transcriptional regulation of other bacterial genes. When Dr Grandi joined ENI as Head of Biotechnology, he became interested in peptide synthetases, large multi-enzymatic complexes responsible for the synthesis of biologically important peptides carrying non-natural amino acids. He managed to elucidate the complex biochemical events that lead to the synthesis of surfactin, a lipopetide produced as secondary metabolite by Bacillus subtilis. Dr Grandi also dedicated substantial efforts to the construction of B. subtilis recombinant strains for the production of proteins of medical and industrial use, including calcitonin, interleukin 1, human growth hormone, isoamylase and proteases. In particular, the production process of Met-less human growth hormone was brought to Phase III, licensed to the pharmaceutical company Pierrel and the patents subsequently sold to the European Pharmaceutical Company Kabi Vitrum. *Protein Engineering* – As Director of the Biotechnology Center of ENI, Dr Grandi also focused his interest on the application of protein structure information to improve thermal stability and catalytic properties of industrial enzymes. He applied Protein Engineering to rationally design multiple amino acid replacements to increase stability and catalytic activity of B. subtilis neutral protease and Pseudomonas isoamylase. In addition, he engineered an E. coli strain capable of converting, with high efficiency, racemic hydantoines into optically pure D-amino acids, key compounds for the synthesis of semi-synthetic b-lactam antibiotics. *Vaccinology* – After joining Chiron/Novartis, Dr Grandi led several successful research projects in the vaccine field. Dr. Grandi has been instrumental for the identification of the HCV receptor (Pileri et al., Science, 1998) and for the elucidation of its 3D structure (Kitadokoro K, EMBO J., 2001). Dr Grandi has been one of the key persons to conceptualize the exploitation of genomic and post-genomic technologies in vaccine discovery. The approach, today universally known as “Reverse Vaccinlogy”, has led to the development of a vaccine against Meningococcus B (Pizza et al., Science, 2000) that is now registered in Europe. The power of the approach was subsequently successfully demonstrated on a second important human pathogen, Group B Streptococcus (Maione et al., Science, 2005). Interestingly, the approach led to the discovery of pilus-like structures, never described before in Streptococci (Lauer et al., Science, 2005). After the successful application of Reverse Vaccinology, Dr Grandi worked on developing more rational approaches to vaccine discovery. First, he showed how the use of DNA microarrays can facilitate the identification of protective antigens by selecting virulence factors specifically expressed during infection (Grifantini et al., Nature Biotechnology, 2003). Subsequently, he developed new proteomic-based strategies to selectively identify surface-exposed protective antigens (Rodriguez-Ortega et al., Nature Biotechnology, 2006; Doro et al., Mol.Cell.Proteomics, 2009; Ferrari et al, Proteomics, 2006; Berlanda Scorza et al., Mol.Cell.Proteomics, 2008). More recently, Dr Grandi has conceptualized a highly selective platform for vaccine discovery, which allows singling out, in an extremely precise manner, the few protective antigens to be used as vaccines (Bensi et al., Mol. Cell. Proteomics, 2012). The platform represents a quantum leap in vaccine research and is expected to highly accelerate the time required to move from laboratory to human trials. Finally, Dr Grandi has recently demonstrated the applicability of Reverse Vaccinology for the identification of antigens inducing cell-mediated immune responses (Finco et al., PNAS, 2011).
	Premi e riconoscimenti
	Nominations and other commitments 2014 In 2014 The Italian Ministry of Research and University (MIUR) has nominated Guido Grandi Full Professor in: 1) Microbiology and Clinical Microbiology; 2) Genetics and Microbiology; 3) Molecular Biology 2013 Winner of the prestigious ERC (European Research Council) advanced investigator grant. The grant has officially started June 1st 2014 and will cover a five-year research project on a highly innovative vaccine platform. 2012-present Member of the Scientific Advisory Board of CNR (National Research Council) 2010 Ad hoc reviewer of "ERC Advanced Grants” proposals 2010 Reviewer of US-NIAID research funding program "Partnerships for Biodefense” 2010 Member of the Scientific Advisory Board of the Forschungszentrum Jülich for the "Medical Infection Genomics", Germany 2009-present Permanent member of the Department for Biomedical Research Peer Review Panel of the VIB Research Institute in Life Sciences in Flanders, Belgium 2009-present Member of the Microbiology, Immunology and Infection Panel of French Research Agency 2009-present Member of the “Target Selection Board” of the American Structural Genomics Centers for Infectious Diseases (SSGCID/CSGID) (Seattle and Chicago, USA) 2008-present Expert for the evaluation of research proposals at Inserm laboratories, France 2007-2010 Expert Reviewer for ERA-NET Pathogenomics projects funded by the European Community 2007-present Founder and member of the Scientific Advisory Board of Externautics SpA, a Biotech Company involved in the discovery of new tumor markers and in the development of new anti-cancer therapeutic and diagnostic products 2000 Expert Reviewer of the European Commission Grant applications 1999 – 2003 President of AIBB (Italian Association of Biocatalysis and Bioseparations) Awards and recognitions 2008 Elected Member of EMBO (European Molecular Biology Organization) 2008 Elected member of the Advisory Board of Faculty of 1000 2010 Recognized as “scientist who has significantly contributed to the field of Vaccinology” by the international Journal “Human Vaccines” that has dedicated Dr. Grandi a bibliographic article