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Unit of Eucariotic Molecular Biology

Lab of Eucariotic Molecular Biology

tel. +++39-0512094146

fax +++39-0512094286

Group Leader: Marialuisa Melli

E-mail : marialuisa.melli@unibo.it

RU Melli

Research in progress :

- Molecular basis of EPM1 - Cystatin B is an antiprotease that inhibits cathepsins. Mutations of the cystatin B gene are found in EPM1. Using the yeast two-hybrid system we have identified seven proteins interacting with cystatin B in a multiprotein complex assembled in the neuronal cytoskeleton. Cytoskeletal cystatin B is polymeric. We are comparing the interactions of the wild type cystatin B with those of the natural mutants obtained from EPM1 patients.

- Role of Tollip in the pathway of IL-1 signal transduction - The Tollip protein mediates the interaction between IRAK-1 and the IL-1 receptor. Tollip’s role in the IL-1 signal transduction pathway is still unclear. By means of the yeast two-hybrid system we have identified several interactors of Tollip now under scrutiny. Results suggest its involvement in the process of protein sumoylation, and the regions of Tollip necessary to its role in sumoylation have been identified.

- Regulation of the biological activity of SOX factors - Although members of the SOX family of transcription factors play key roles during embryo development, little is known about the molecular mechanisms modulating their biological function. We have recently shown that post-translational modifications, such as sumoylation and phosphorylation, affect SOX2 and SOX10 stability, and we are currently investigating whether or not these modifications affect differentiation of glial or osteoblast cells, respectively.

Funding :

- PRIN 2003-2005 (MIUR)

- FIRB

- Telethon 2003-2006

Patents :

-

Selected Publications :

-Strazza M., Luddi A Brogi A. Carbone M., Riccio M., Santi S., Melli M and Costantino-Ceccarini E. 2004 Activation of cell cycle regulatory proteins in the apoptosis of terminally differentiated oligodendrocytes. Neurochemical Research 29, 923-931

-Blasi F, Ciarrocchi A, Luddi A, Strazza M, Riccio M, Santi S, Arcone R, Pietropaolo C, D'Angelo R, Costantino-Ceccarini E, Melli M. 2002 Stage specific gene expression in early differentiating oligodendrocytes. GLIA 39: 114-123

-Di Giaimo R, Riccio R, Santi S, Galeotti C,. Ambrosetti DC, Melli M. 2002 New insights into the molecular basis of Progressive Myoclonus Epilepsy (EPM1): a multiprotein complex with cystatin B. Human Molecular Genetics 11: 2941-2950

-Riccio M., Di Giaimo R, Pianetti S, Palmieri PP, Melli. M, Santi S. 2001 Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonous epilepsy (EPM1). Experimental Cell Res. 262: 84-94

-Falugi F,. Petracca R,. Mariani M, Luzzi E, Mancianti S.,. Carinc V., Melli M, Finco O,. Wack A, Di Tommaso A.,. Costantino P, Del Giudice G., Abrignani S, Rappuoli R,. Grandi G. 2001 Rationally designed strings of promiscuous CD4(+) T cell epitopes provide help to Haemophilus influenzae type b oligosaccharide: a model for new conjugate vaccines. European J. Immunol 3816-3824

-Ambrosetti DC, Scholer HR, Dailey L, Basilico C. 2000 Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer. J Biol Chem. 275: 23387-97

-Blasi F., Riccio M., Brogi A., Strazza M., Taddei ML., Romagnoli S., Luddi A., D’Angelo R., Santi S., Costantino-Ceccarini E., Melli M. 1999 Constitutive expression of Interleukin-1b (IL-1 b) in rat oligodendrocyte. Biol. Chem. 380: 259-264

-Sahni M, Ambrosetti DC, Mansukhani A, Gertner R, Levy D, Basilico C. 1999 FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway. Genes Dev. 13, 1361-66

-Riccio M, Santi S, Dembic M, Di Giaimo R, Cipollini E, Costantino-Ceccarini E, Ambrosetti DC, Maraldi NM, Melli M. - Cell-specific expression of the epm1 (cystatin B) gene in developing rat cerebellum. Neurobiology of Diseases: in press -

-Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, and Basilico C. - Sox2 induction by FGF AND FGFR2 activating mutations interferes with WNT signaling and inhibits differentiation in osteoblasts. Mol. Cell. Biol.: In press -

Postgraduate training :

- PhD Programme in Cellellular, Molecular and industrial Biology (Project n.1: Physiology and Cellular Biology)

- Post doctoral fellowships on specific research projects

Collaborations :

- : Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.

- : Laboratorio di Biologia Cellulare e Microscopia Elettronica, I.O.R., 40136 Bologna, Italy

- : Department of Genetics and Molecular Biology, Federico II University, Naples, Italy

- : Istituto di Fisiologia Clinica CNR Siena, I-53100, Siena, Italy

Links :

Post-graduate training
http://www.dipartimentobiologia.it/doctoraltraining/melli.asp

Research group :

Marialuisa Melli  (Full professor)

Davide Ambrosetti  (Research Associate)

Valentina Sancisi  (PhD student)

Elena Cipollini  (PhD student)