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Laboratory of Protein Biochemistry and Pathology of Protein Misfolding Diseases

Vittorio Bellotti
Monica Stoppini
Patrizia Mangione
Sofia Giorgetti

Protein misfolding diseases are becoming a prominent category of human diseases and include Alzheimer’ disease, prion protein diseases, systemic amyloidosis. Our research group has a long tradition of protein biochemistry, established by our master and former director Prof. Giuseppina Ferri, and is now fully dedicated to the characterization of the structural bases of pathologic conversion of human globular protein into amyloid fibrils. This research requires a wide technological approach that includes: 1) all the techniques necessary for basic protein biochemistry, production of recombinant proteins and their chemical characterisation 2) a large number of spectroscopic techniques for protein function and folding studies at the equilibrium or in fast dynamic conditions 3) the access to the laboratories of colleagues in the University of Udine for carrying out NMR spectra of proteins in solution. Through this approach the laboratory was able in last few years to elucidate a few structural, kinetic and thermodynamic aspects of the mechanism of fibril formation of three prototypic amyloidogenic human proteins such as lysozyme, beta 2-microglobulin and apolipoprotein A-I. The laboratory is now involved in a project dedicated to the characterisation of the mechanism of tissue specificity of amyloid diseases in which proteomic studies on natural proteins are linked to the biophysical investigation of isolated proteins or protein in complex with natural ligands. The characterization of new molecular targets is parallel to the identification of new synthetic ligands of potential pharmaceutical interest for the treatment of systemic amyloidosis. The identification of specific protein ligands of potential pharmaceutical interest is carried through the access to a chemical library shared with the Department of Pharmaceutical Chemistry and the collaboration with an USA company.

Fig 1. Proteomics of amyloid tissue. Fig 2. Molecular structure of amyloid fibrils.



Members of the team
Vittorio Bellotti MD-PhD(Professor of Biochemistry) vbellot@unipv.it
Monica Stoppini PhD (Professor of Biochemistry) stoppini@unipv.it
Patrizia Mangione PhD (Professor of Biochemistry) p.mangione@unipv.it
Sofia Giorgetti PhD ( Lecturer in Biochemistry) s.giorgetti@unipv.it
Sara Raimondi PhD ( Research fellow) sara.raimondi@unipv.it
Sara Marini PhD (Research fellow) saramarini77@virgilio.it
Loredana Marchese (PhD student) loredanamarchese@libero.it
 

Department of Biochemistry-Biotechnology Laboratories IRCCS San Matteo
Faculty of Pharmacy
Via Taramelli, 3/b Pavia
TEL. 0382.502984
E-MAIL: vbellot@unipv.it

 

Selected publications

Booth, D.R., Sunde, M., Bellotti, V., Robinson, C.V., Hutchinson, W.L., Fraser, P.E., Hawkins, P.N., Dobson, C.M., Radford, S.E., Blake, C.C., Pepys, M.B. Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 385:787-793, 1997.

Esposito G., Garcia, J., Mangione, P., Giorgetti, S., Corazza, A., Viglino, P., Chiti, F., Andreola, A., Dumy, P., Booth, D., Hawkins, P.N., Bellotti, V. Structural and folding dynamic properties of the T70N variant of human lysozyme. Journal of Biological Chemistry 278:25910-25918, 2003

Merlini, G., Bellotti, V. Molecular mechanisms of amyloidosis. New England Journal of Medicine 349:583-596, 2003

Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 440:1217-21, 2006

Relini A, Canale C, De Stefano S, Rolandi R, Giorgetti S, Stoppini M, Rossi A, Fogolari F, Corazza A, Esposito G, Gliozzi A, Bellotti V. Collagen Plays an Active Role in the Aggregation of beta2-Microglobulin under Physiopathological Conditions of Dialysis-related Amyloidosis. Journal of Biological Chemistry. 281:16521-9, 2006

International collaborations

Prof. Mark Pepys The Centre for Amyloidosis and Acute Phase Proteins
http://www.ucl.ac.uk/medicine/amyloidosis/

Prof. Chris Dobson Chemistry Laboratories University of Cambridge
http://www.ch.cam.ac.uk/staff/cmd.html

Prof. Lode Wyns Department of Molecular and Cellular Interactions VIB, the Flanders Interuniversity Institute for Biotechnology Bruxelles
http://www.vib.be/VIB/EN/

         

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