Study o of structure-function relationship in proteins  mainly by the X-ray crystallography with the aim to find new inhibitors of the studied enzymes to be used as lead compound for drug design.

Andrea Ilari obtained the structures by X-ray crystallography of different proteins:

1)E. coli flavohemoglobin and of the following truncated hemoglobins: Bacillus subtilis truncated hemoglobin  and Thermobifida fusca truncated hemoglobin. The structural analyses disclosed the role of these protein in the protection mechanism of bacteria from oxidative damage.

2)Sorcin  (SOluble Resistance related Calcium bInding proteiN) a protein involved in excitation-contraction-relaxation processes in the heart through the interaction with several Ca2+ channels.

3) Studies of the molecular mechanism of MuntiDrug Resistance in cancer cell involving Sorcin.

3)Dps (DNA binding proteins from starved cells)  cage-like proteins involved in the bacterial-DNA protection from oxidative damage and used as bioreactor to produce metal-based nanoparticles. 

4)Structure of the proteins involved in the trypanothione metabolism, a molecule which protect the Leishmania parasites (responsible for Leishmaniasis) from the ROS (Reactive Oxygen Species) produced by macrophages during the infection . 

5)ZnuA, the periplasmic component of the bacterial zinc transporter ZnuABC.  The study aims at designing a new antibiotic against Salmonella enterica which, as all the gram negative bacteria, develops very easily drug resistance. 

6) Identification of molecular markers of Huntington Disease a neurodegenerative disease due to a mutation in the Huntingtin gene.

1: Ilari A, Fiorillo A, Poser E, Lalioti VS, Sundell GN, Ivarsson Y, Genovese I,  Colotti G. Structural basis of Sorcin-mediated calcium-dependent signal transduction. Sci Rep. 2015 Nov 18;5:16828.

2: Kasyutich O, Ilari A, Fiorillo A, Tatchev D, Hoell A, Ceci P. Silver ion incorporation and nanoparticle formation inside the cavity of Pyrococcus furiosus ferritin: structural and size-distribution analyses. J. Am. Chem. Soc., 2010, 132(10):3621-7. 

3: Baiocco P, Colotti G, Franceschini S, Ilari A. “Molecular basis of antimony treatment in leishmaniasis.” J Med Chem., 2009; 52(8):2603-12. 

4: Ilari A, Franceschini S, Bonamore A, Arenghi F, Botta B, Macone A, Pasquo A, Bellucci L, Boffi A. “Structural basis of enzymatic (S)-norcoclaurine biosynthesis.” J Biol Chem. 2009; 284(2):897-904.  

5: Ilari A., Ceci P., Ferrari D., Rossi G.L., Chiancone E.,”Iron incorporation into Escherichia coli Dps gives rise to a ferritin-like microcrystalline core” J. Biol. Chem.,277, 37619-23, (2003).

6: Ceci P.,  Ilari A.,  Falvo E.,  Chiancone E., “The Dps protein of Agrobacterium tumefaciens does not bind to DNA but protects it toward oxidative cleavage: X-ray crystal structure, iron binding, and hydroxyl-radical scavenging properties.”J. Biol. Chem., 278, 20319-26, (2003). 

7: Zhao G., Ceci P., Ilari A., Giangiacomo L., Laue T.M., Chiancone E., Chasteen N.D. “Iron and hydrogen peroxide detoxification properties of DNA-binding protein from  starved cells. A ferritin-like DNA-binding protein of Escherichia coli.” J Biol Chem. 2002; 277(31):27689-96.

8: Ilari A., Bonamore A., Farina A., Johnson .K. A., Boffi A., “ The X-ray structure of E. Coli flavohemoglobin reveals an unexpected geometry of the distal heme pocket.”, J. Biol. Chem., 277, 23725-32, (2002).

9: Ilari A., Johnson K. A., Nastopoulos V., Verzili D., Zamparelli C., Colotti G.,Tsernoglou D. and Chiancone E., “The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein”, J. Mol. Biol., 317, 447-458, (2002).

10: Ilari, A., Stefanini, S., Tsernoglou, D., and Chiancone E., “ The dodecameric ferritin from L. innocua contains a novel intersubunit iron-binding site”, Nature Struct. Biol., 7, 38-43,  (2000).

Annarita Fiorillo, Postdoc, Dip. Scienze Biochimiche Università Sapienza

Paola Baiocco, Postdoc, Dip. Scienze Biochimiche Università Sapienza

Dott. Ferdinando Squitieri, Casa Sollievo della Sofferenza e CSS-Mendel

Prof.ssa Emilia Chiancone, Prof. emerito, Dip. Scienze Biochimiche

Prof. Alberto Boffi, Dip. Scienze Biochimiche, associato IBPM

Prof. ssa Beatrice Vallone, Dip. Scienze Biochimiche, associato IBPM

Dottoressa Marina Gramiccia, Istituto Superiore di Sanità

Dott. Marco Lalle, Istituto Superiore di Sanità

Dott. Luca Vannucci, Institute of Microbiology Academy of Sciences Czech Repubblic

Dott. Vassiliki Lalioti, CSIC, Madrid, Spain

EDUCATION

1998 - Ph.D. in Biophysics at the University of Roma  “La Sapienza”. Dissertation:”Metal binding proteins: (a) "Sorcin (SOlubile Resistance related Calcium-bInding proteiN), a penta-EF calcium binding protein with a role in the calcium-mediated intracellular signal transduction"; (b) "Crystallization and preliminary X-ray diffraction studies on the ferritin from  Listeria innocua"

1997- Research training in “Crystallization of hemoproteins in presence and absence of oxygen”, Prof. W. E. Royer, Medical Center, University of Massachusetts, Worcester, USA.. 

1993 - Laurea in Chemistry, summa cum laude, at the University of Roma “La Sapienza”. Thesis :” "Heme- protein interactions in the Horse spleen Myoglobin and in the homodimeric hemoglobin from Scapharca inaequivalvis. Fluorescence and optical absorption studies on the proteins reconstituted with Zn- e Protoporfirin IX";

in 1987: High school Diploma,  Liceo Scientifico Statale "C. Cavour" of Roma.

PROFESSIONAL EXPERIENCE:

Since January 1th 2007: first researcher at the “Istituto di Biologia e Patologia Molecolari”, Centro Nazionale delle Ricerche (Italian Research National Council).

2001-2007 : Research fellow at the “Istituto di Biologia e Patologia Molecolari”, Centro Nazionale delle Ricerche (Italian Research National Council).

1999-2001  Research fellowship: “Crystallization of macromolecules in microgravity”, at the “Istituto di Biologia e Patologia Molecolari”, Centro Nazionale delle Ricerche (Italian National Research Council) in collaboration with the ASI (Italian Space Agency) (projects ASI/ARS-99-22, ASI/I/R/28/00)

1999 –Research fellowship : “Structural dynamics of nitrite reductase”. In collaboration with the “Centre National de la Recherche scientifique”- Laboratoire de Cristallographie et Cristallisation des Macromolécules Biologiques – Marseille (France) on the project .

1998 –Post-doctoral fellowship: “Research on resistance-related proteins of Mycobacteria”, Dep. of Genetics and Microbiology ,University of Pavia, Italy.

TEACHING ACTIVITY

2014-2017 From 2104 is a member of the committee of the Ph.D. in Biochemistry of the Department of biochemical Sciences of the Sapienza  University of Roma. 

2011 – Lecturer of the Practical Course “Bioinformatic Applications in  Structural and Molecular Biology” organized for the Ph.D student in Biochemistry of the Department of Biochemical Sciences , University of L’Aquila.

2010 – 19/10-4/11. : Lecturer of the Practical Course “Bioinformatic Applications in  Structural and Molecular Biology” for the personnel of the Institute of Molecular Biology and Pathology, CNR. 

2002-2010: Lecturer of the Course of stoichiometric calculations  for undergraduate students, laurea in “Tecnico di Laboratorio Biomedico”,  Medicine and Surgery Faculty, University of Roma “La Sapienza” 

2002-2010:Lecturer of the Course of stoichiometrical calculations  for undergraduate students, laurea in Medicine and Surgery Faculty, University of Roma “La Sapienza” . 

2007: Lecturer of the Practical Course “From the protein crystallization to the protein structure determination”, for the personnel of the Institute of Molecular Biology and Pathology, CNR.

RESEARCH PROJECTS

 2017 – Research unit coordinator of the project IBPM-CNR: “Understanding the 3D structure of a variety of proteins related to the human health” of the “Crystallography BAG Beam Time at the ESRF”, main proposer Prof. Giuseppe Zanotti.

2015-2017 Research unit coordinator of the project: COLLEZIONE DI COMPOSTI CHIMICI ED ATTIVITÀ DI SCREENING - Studi strutturali e funzionali sugli enzimi del metabolismo del tripanotione e delle poliammine, bersagli molecolari per la sintesi di nuovi farmaci contro la leishmaniosi.   CUP: B56G1500114000

2014-2015 Research unit coordinator of  the Biocrystal Facility, modulo SV.P14.008.001-GAE P0000182.

2014-2015 Research unit coordinator of  the Biocrystal Facility, modulo SV.P14.008.001-GAE P0000182.

2014 - CMST COST Action CM1307 WG1 Targeted chemotherapy towards diseases caused by endoparasites

2013- Biocrystallography research unit coordinator of IBPM for the  project BiostructX_3959

2013 - Helmholtz Centrum Berlin (Bessy) coordinator of  the project 2013_2_130059:X-ray structure of proteins involved in the dithiol redox metabolism of Leishmania

2012 - Biocrystallography research unit coordinator of IBPM for the project BiostructX_1223.2 “Structural characterization of trypanothione metabolism in Leishmania spp”

2012 - Biocrystallography research unit coordinator of IBPM for the project BiostructX_1223.8: “New drugs for old bugs: targeting the Zn importing system of Salmonella enterica”.”

from 2012- coordinator of the structural biology unit for the project: “Novel redox sensing pathways in parasitic microorganisms”, finanziato dall'Istituto Pasteur, Fondazione Cenci Bolognetti, principal investigator prof. Alberto Boffi.

2012 -  Helmholtz Centrum Berlin (Bessy) coordinator of  the project 2012_2_120100: X-ray structures of enzymes and macromolecular complexes essential to survival and virulence of pathogenic bacteria in the human host and potential targets for development of new antibiotics.

2009-2011 – Member of operative unit in the project ”Inhibition of the bacterial high affinity Zn-uptake system: a novel strategy for the design of antimicrobial agents”.  Fondazione Roma

2007-2008 – Member of operative unit in the project MIUR-PRIN “ Roles of sorcin supramolecular complexes  in the regulation of the Ca(II)-dependent cellular function “

Coordinator of the project:Vincenzo Sorrentino 

2005-2006 Member of operative unit in the project MURST-PRIN: “Supramolecular assemblies. The Dps (DNA-binding proteins from starved cells)-DNA and sorcin-calcium channels systems and their biological function”

Coordinator of the project: E. Chiancone

2003-2005 Member of operative unit in the project FIRB 2003 “Novel environment friendly biotransformations and optimization of industrial processes based on the use of enzymes and organometallic catalysts”. 

Coordinator of the project :Prof. A. Boffi

Project code: RBNE034XSW

2003-2004 Member of operative unit  in the project MURST PRIN  dal titolo “Structural Biology and dynamics of redox proteins. Dps  (DNA binding Proteins from Starved cells): redox properties of their complexes with iron ions, DNA binding and protection against oxidative damage”. Prot.003050 74_005

Coordinator of the project: Prof. A Coda 

1998-2002 Member of operative unit  in the project ASI (Agenzia Spaziale Italiana) “Macromolecules in Microgravity: crystal growth of proteins relevant to biomedicine and biotechnology” 

Coordinator of the project: Prof. M. Bolognesi.

Project codes: ASI/ARS-98-59, ASI/ARS-99-22, ASI/I/R/28/00, ASI IR/167/2001, ASI: I/R/294/02

2001-2003 Member of operative unit  in the project FIRB 2001 “Roles of transition metals and of metalloproteins in the infection by intracellular bacteria and possible therapeutic implications” . 

Coordinator of the project: Prof. E. Chiancone.

Project code:RBAU01YMTR

2001-2002 Member of operative unit  in the project MURST-PRIN “Structural biology and structural dynamics of redox proteins.– The complexes of the ferritin  from Listeria innocua with iron and the E. coli Dps, a protein overexpressed under oxidative stress: redox properties and biological role”. 

Coordinator od the project:Prof. A. Coda

Project code:2001054582_006

2000 – Coordinator of the project ” Supramolecular assemblies. Dps-Fe(II) complexes and their role in the DNA protection from oxidative damage” 

Project code: CNRG0015A2

1999-2000 Member of operative unit in the project MURST-PRIN, “Structural biology and structural dynamics of redox proteins. – The ferritin from Listeria innocua a structural homolog of the Dps proteins able to oxidize and incorporate iron”. 

Project code: 9905228975_003

Coordinator of the project: Prof. Alessandro Coda 

1997-1998 Member of operative unit  in the project MURST-PRIN: “Structural Biology–Oligomeric proteins, stability of the quaternary structure and functional regulation”

Coordinator of the project: Prof. A. Coda

1996 Member of operative unit  in the project MURST-PRIN. “Structural biology and structural dynamics of redox proteins”.

Coordinator of the project: Prof. A. Coda

1995 Member of operative unit  in the project “Structural  organizations of proteins. Subunit interactions and functional regulation in oligomeric proteins.”

Coordinator of the project: Prof. A. Coda

PEER REVIEWING

2011- Peer reviewer for: Plosone, Bioorganic Medicinal Chemistry Letters and ACS Medicinal Chemistry Letters

2009 – Peer reviewer for: FEBS J. and International Journal of Parasitology

2008 –Peer reviewer  for: Acta Cryst. Section F: Structural Biology and Crystallization communications, editor Dr H.M. Einspahr.

         - Peer reviewer for the project “Japanese-Swiss Science and Technology Cooperation Program in Medical Research”, su richiesta della Dr. Rahel Byland, Projekt Koordinatorin Japan und Korea

International Institutional Affairs ETH-Zentrum

Dal 2001 Responsabile del servizio di cristallografia dell’IBPM insieme alla dottoressa Linda Savino (http://www.ibpm.cnr.it).

SCIENTIFIC CONFERENCE ORGANIZATION

1999 – Andrea Ilari was in the organization commettee of the congress “Biocrystallography for Medicine and Biotechnology” Roma - Auditorio dell’Accademia Nazionale dei Lincei.

INVITED LECTURES

2011 “New drugs for neglected diseases”, Medicinal Chemistry in Parasitology 2011, Modena,  5-7 October 2011. “X-ray structures of the trypanothione metabolism proteins, potential drug targets against Leishmaniasis. Gianni Colotti, Paola Baiocco, Annarita Fiorillo, Andrea Ilari

2010 13th International Symposium on Molecular Medicine, Hotel Poseidon Resort, Loutraki, Greece, 7-9 October. “ZnuA, the soluble component of the bacterial Zn(II) ABC transporter, a possible target for novel antibiotics”  Flaminia Alaleona, Roberto Di Santo Emilia Chiancone Andrea Ilari.

2009 12th International Symposium on Molecular Medicine, Hotel Poseidon Resort, Loutraki, Greece, 15-17 October. “The X-ray structure of trypanothione reductase in complex with NADPH and Sb(III) discloses the molecular basis of antimony treatment in leishmaniasis” Paola Baiocco, Gianni Colotti and Andrea Ilari

1999 Sorrento, Italy, 23-27 May: Bioiron, World Congress on Iron Metabolism. “X-ray structure of the dodecameric ferritin from Listeria innocua related to the DNA-Binding Proteins of the Dps family” A. Ilari, E. Chiancone, S. Stefanini, and D. Tsernoglou.

PROGRAM CHAIR:

2009- Session of “Microbiology” del 12th International Symposium on Molecular Medicine, Hotel Poseidon Resort, Loutraki, Greece, 15-17 October.

SCIENTIFIC AWARDS

2009-  Scientific award from the CNR President Luciano Maiani for the innovative results in research, reached in 2005.

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OTHER ACTIVITIES:

2012- Editorial member of Journal of Biological Research (ISSN 2225-3203)

2009 14-19 april Festival of Science  of the Municipio Roma III, Scienza III. 

Organizator of  a practical course of protein crystallization for students of elementary schools.

2008. 14-16 november. Member of the project “From information to function”, selected for the partecipation to the ”European City of Science”, Scientific festival for science dissemination.  Paris - France. 

Patent

Piera Valenti, Tiziana Natalizi, Roberto Di Santo, Luca Pescatori Giuliana Cuzzucoli Crucitti, Emilia Chiancone, Andrea Ilari: Pirrolil-idrossammati per uso nella prevenzione e/o nel trattamento di infezioni batteriche. Depositato il 6 giugno 2012 al numero MI2012A000980.

Books chapters

2017- Ilari A, Savino C. A Practical Approach to Protein Crystallography. Methods Mol Biol. 1525:47-78. 

2015 -A. Ilari, A. Bonamore, and A. Boffi  « Addition to C=N Bonds”, Book title: “Biocatalysis in Organic Synthesis 2”, Science of Synthesis (SOS) 2014-2016, Editor Thieme Chemistry.

2011- Pierpaolo Ceci, Veronica Morea, Manuela Fornara, Giuliano Bellapadrona, Elisabetta Falvo and Andrea Ilari “Biomimetic materials synthesis by ferritin-related, cage-shaped proteins”, Book title “Biomineralization”, 2011, Editor Intech - Open Access Publisher.

2009 -Stefanini S., Ceci P., Ardini M., Ilari A.: DNA-binding proteins from sterved cells, Handbook of metalloproteins, edited by Prof. Messerschmidt, John Wiley & Sons, Ltd.

2008- Ilari A, Savino C. “Protein structure determination by X-ray crystallography.”  Book title: “Bioinformatics: Data, Sequence Analysis and Evolution”, Editor Jonathan M. Keith, Series: Methods in Molecular Biology, Volume 452, pages 63-87.