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INIZIO_TESTO_DA_INDICIZZARE

Fund for investing in fundamental research

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Research Units
  • Libera Universita' "Vita Salute S.Raffaele" MILANO
    Dip. MEDICINA E CHIRURGIA , MILANO (MI)
  • FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR
    DIBIT , MILANO (MI)
  • ISTITUTO EUROPEO DI ONCOLOGIA
    Oncologia Sperimentale , MILANO (MI)
  • Libera Universita' "Vita Salute S.Raffaele" MILANO
    Dip. MEDICINA E CHIRURGIA , MILANO (MI)
  • IFOM, ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
    Istituto FIRC di Oncologia Molecolare , MILANO (MI)
  • Universita' degli Studi di PADOVA
    Dip. CHIMICA BIOLOGICA , PADOVA (PD)
  • Universita' degli Studi di GENOVA
    Dip. MEDICINA SPERIMENTALE , GENOVA (GE)
  • Nerviano Medical Science S.r.l.
    ricerca e sviluppo , MILANO (MI)
Similar FIRB:
Scientific and education field classification
International Patent Classification
  • CHEMISTRY; METALLURGY
    • BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
      • MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF (biocides, pest repellants or attractants, or plant growth regulators, containing micro-organisms, viruses, microbial fungi, enzymes, fermentates or substances produced by or extracted from micro-organisms or animal material A01N63/00; food compositions A21, A23; medicinal preparations A61K; chemical aspects of, or use of materials for, bandages, dressings, absorbent pads or surgical articles A61L; fertilisers C05); PROPAGATING, PRESERVING OR MAINTAINING MICRO-ORGANISMS (preservation of living parts of humans or animals A01N1/02); MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (micro-biological testing media C12Q)
Geographical classification
Bibliografia
3.2.a. Riferimenti bibliografici (max 1 pag. = 8000 caratteri).
1. Blasi, F. Immunol. Today, 18, 415-417, 1997.
2. Ossowski, L. e Aguirre Ghiso, J. Curr. Opin. Cell Biol. (2000) 12, 613-620.
3. Calpaina
4. Weissman, A. M. (2001) Nat Rev Mol Cell Biol 2, 169-178
5. Hicke, L. (2001) Nat Rev Mol Cell Biol 2, 195-201
6. Laney, J. D. and Hochstrasser, M. (1999) Cell 97, 427-430
7. Hicke, L. (2001) Cell 106, 527-530
8. Katzman, D.J., Babst, M. and Emr, S.D. (2001) Cell 106, 145-155
9. Hofmann, K. & Falquet, L (2001) Trends Biochem Sci 26, 347-350
10. van Delft, S., Govers, R., Strous, G.J., Verkleij, A.J. and van Bergen en Henegouwen, P. M. (1997) J Biol Chem 272, 14013-14016
11. Coda, L., Salcini, A.E., Confalonieri, S., Pelicci, G., Sorkina, T., Sorkin, A., Pelicci, P.G. and Di Fiore, P.P (1998) J Biol Chem 273, 3003-3012
12. Matsuzawa, S., Takayama, S., Froesch, B.A., Zapata, J.M. and Reed, J.C. (1998) Embo J, 17, 2736-2747.
13. Schwechheimer C. and Deng X. Trends Cell Biol. 2001. 11:420-426
14. Mann M, Hendrickson RC, Pandey A. Annu Rev Biochem. 2001 Jul 10;70:437-473.).
15. Shevchenko A, Chernushevich I, Wilm M, Mann M. Methods Mol Biol. 2000;146:1-16.
16. Battistutta R, Sarno S, DeMoliner E, Zanotti G, Pinna LA (2000) J. Biol. Chem. 275, 29618-29622.
17. Brunati AM, Bordin L, Clari G, James P, Quadroni M, Beritono E, Pinna LA, Donella-Deana A (2000) Blood 96, 1550-1557.
Gygi et al. Nat. Biotech 1999 17 10 994 /999
Keywords
Plasminogen activators; Calcium-dependent proteases; Ubiquitination; Protease receptors; Protease substrates

PROTEASES IN NORMAL AND PATHOLOGICAL CELL RESPONSES. IDENTIFICATION OF ENDOGENOUS SUBSTRATES AND INDUCED MOLECULAR MECHANISMS.

Libera Università "Vita Salute S. Raffaele" - Milano
Abstract
This project will exploit and set up leading edge technologies to study the role of proteases in normal and pathological cell responses at the proteomic level. This has become possible thanks to the completion of the sequenze of the human genome. Moreover, the project will form an electronic network for the partners with a "Virtual Center" allowing the information and on-line analysis of the results and the sharing of the software for analysis, storage and handling of the data. The choice of the partners, in addition to their scientific excellence, has been based on their scientific and technological convergence as well as on the possibility to transfer the results to the industry.
The project focuses on proteases: five of the Units will analyse in detail various aspects of three types of proteases, while three Units will, in addition, also act as technological motors and provide common excellence services.
The Units of this project will identify new substrates of a serine protease (urokinase), of a calcium-dependent protease (calpain) and of the ubiquitination system. Moreover, new components of the ubiquitin-ligase gene family and other proteins interacting with them will be identified. Moreover, the substrates and the types of protease-induced, or protease-conditioning, post-translational modifications will be analysed. The project aims at obtaining more sensitive and reproducible techniques in the areas of purification of multiprotein complexes>>>

Principal Investigator
FRANCESCO BLASI, Libera Universita' "Vita Salute S.Raffaele" MILANO
Research Goal
The present project is aimed at investigating the role of proteases in both normal and pathological cellular responses. The most recent technologies will be exploited to carry out an in-depth high-throuput study. These technologies are based on one side on the presence in data banks of the nucleotide sequence of the entire human genome (and of a large part of the murine one), and consequently of the amino acids sequence of many proteins. On the other side, they are based on the dramatic improvements in sensitivity and reproducibility of the techniques to purify molecular complexes and to sequence their protein components. It is in fact abundantly clear, that proteins within the cells are present in multi-molecular complexes, the formation of which is essential for the function of the cell. Another important goal is to collect a series of highly qualified laboratories into a single "virtual Centre", allowing both a real-time exchange of information about the results obtained by the various Units and the sharing of dedicated softwares for data processing and analysis.
Finally, the partners were chosen not only on the basis of common fields of interest and scientific excellence, but also to generate results that could be transferred to the pharmaceutical industry. In fact one of the Units belongs to an important pharmaceutical industry, and other Companies have already shown their interest in our project. In addition, since six of the eight participating Units belong to>>>

Timescale
36 months