EDUCATION

1987: Graduated (Laurea) in Biological Sciences, University of Rome “Tor Vergata”
1987-1988: Post-graduation training in the Department of Biology, University of Rome “Tor Vergata”.
1992: Ph.D. in Cellular and Molecular Biology. University of Rome "Tor Vergata".

1992-1996: Post-doctoral fellow.
1) CNRS, Toulouse, France
2) Biological Laboratories, Harvard University, Cambridge, USA
3) European Molecular Biological Laboratory (EMBL), Heidelberg, Germany
 

CAREER

1995-1999 Researcher (Lecturer) in Molecular Biology in the Department of Biology, University of Rome, Tor Vergata, Italy.
1999-2002 Assistant Professor in Molecular Biology in the Department of Biology, University of Rome, Tor Vergata, Italy.
2000 Appointed as Professor at the “Universidad Nacional De Tucuman, Facultad de Bioquimica, Quimica Y Farmacia”. S. Miguel de Tucuman, Argentina.
2002 Associate Professor (tenured) in Molecular Biology in the Department of Biology, University of Rome, Tor Vergata, Italy.
2003 Group leader in the Institute for Neuroscience, Fondazione Santa Lucia, Rome, Italy. Laboratory of Cellular and Molecular Neuroscience.

-Member of the Italian Societies for Molecular and Developmental Biology (FISV, Federazione Italiana Scienze della Vita that includes the mentioned societies).
-Member of the Faculty of 1000 (www.facultyof1000.com).
-Member of the PhD programme in Cellular and Molecular Biology in the Department of Biology, University of Rome “Tor Vergata”.

FUNDING AGENCIES from 1997 to today

- Consiglio Nazionale delle Ricerche
- American Fragile X Syndrome Association

- American National Alliance for Autism Research (NAAR)
- Italian Fragile X Syndrome Association
- Human Frontier Science Program
- Italian National Institute of Health
- Italian Ministry of University
- TELETHON
 

CURRENT RESEARCH AND FUTURE GOALS

One of the big tasks in neuroscience is to understand how a neuronal cell can store previous experience and change its output accordingly: the basis of learning and memory. Recent work has shown that a crucial contribution comes from autonomous protein expression in the periphery of the neuronal cell. Specific mRNAs are transported from the cell body to the axons and dendrites, where they are translated in a regulated manner. Our goal is to understand how this process contributes to learning and memory processes. For this aim, three broad questions have to be addressed: (i) Protein synthesis is typically cytoplasmic – how are the necessary components of the protein synthesis machinery transported to the dendrites/axons? In particular, how are the proper mRNAs selected. (ii) What triggers local protein synthesis? (iii) What downstream effects has this regulated translation?

Over the last five years, my lab has been studying the cause of the Fragile X syndrome. The Fragile X Syndrome is the most frequent cause of inherited mental retardation (1:2500 males, 1:4000 females) and is linked to the absence of the Fragile X Mental Retardation Protein FMRP. FMRP belongs to the family of RNA-binding proteins and has been implicated in translational control, but it is not understood how the absence of a translational regulator like FMRP could lead to a deficit in learning and memory and mental retardation. In fact, the study of the mental retardation protein FMRP touches all aspects of local translation at the synapses and therefore offers a major inroad into the understanding of this process.

1. Dendritic RNA/mRNA transport.
Synaptic protein synthesis is the final process of a multistep regulatory mechanism involving dendritic mRNA targeting and localization. For only few of these mRNAs it has been shown that cis-acting signals (3'UTR) mediates the targeting. We are focusing our interest on selected dendritic mRNAs among them FMR1 mRNA which encodes for the Fragile X Mental Retardation Protein, FMRP.

2. Regulation of local protein synthesis.
In order to study mRNA translation at the synapses, we have established an improved method for preparing synaptosomes from mouse brain. We have shown that protein synthesis occurs at the synapses and for some mRNAs it changes upon chemical stimulation. We have investigated the function of FMRP at synapses and show that FMRP acts as a translational repressor of specific mRNAs. We are currently elucidating how FMRP exerts this effect through characterization of the binding partners involved in translation.
 

PUBLICATIONS

1) Mariottini, P., Bagni, C., Annesi, F. and Amaldi, F. (1988). "Isolation and nucleotide sequences of cDNAs for Xenopus laevis ribosomal protein S8: similarities in the 5' and 3' untranslated regions of mRNAs for various r-proteins". Gene, 67, 69-74.

2) Bagni, C., Mariottini, P., Annesi, F. and Amaldi, F. (1990). "Structure of Xenopus laevis ribosomal protein L32 and its expression during development". Nucleic Acid Res. 18, 4423-4426.

3) Mariottini, P., Annesi, F., Bagni, C., Chen Q.M., Francesconi, A., Pesce, C.D., Serra, M.J. and Amaldi, F. (1990). "Ribosomal protein genes in Xenopus laevis: organization, structure and identification of the cis-element responsible for their translational control". in "Nuclear structure and function". J.R. Harris ed., Plenum Publishing Co., New York, pp. 83-87.

4) Bagni, C., Mariottini, P., Terrenato, L. and Amaldi, F. (1992). "Individual variability in the translational regulation of ribosomal protein synthesis in Xenopus". Mol.Gen.Genet. 234, 60-64.

5) Chen, Q.M., Mariottini, P., Bagni, C. and Amaldi, F. (1992). "The pyrimidine sequence encompassing the transcription start point of Xenopus laevis genes encoding ribosomal proteins is not obligatory for the activity in oocytes" Gene 119, 283-286.

6) Mariottini, P., Bagni, C., Francesconi, A., Cecconi, F., Serra, M.J., Chen, Q.M., Loreni, F., Annesi, F. and Amaldi F. (1993). "Nucleotide sequence of the gene coding for the ribosomal protein S8 of Xenopus laevis". Gene 132, 255-260.

7) Bagni C., Mariottini P., Annesi F., Amaldi F. (1993). “Human ribosomal protein L4: cloning and sequencing of the cDNA and primary structure of the protein”. Bioch.Bioph.Acta 1216, 475-478.

8) Girard J.P., Bagni C., Caizergues-Ferrer M., Amalric F. and Lapeyre B. (1994). “Identification of a segment of the snoRNP protein GAR1 which is sufficient for nucleolar accumulation”. J.Biol.Chem. 269, 18499-18506.

9) Hsu T.*, Bagni C*., Sutherland J. and Kafatos F.C. (1996). "The transcription factor CF2 is a mediator of EGF-R activated dorsoventral patterning in Drosophila Oogenesis". Genes & Dev 10, 1411-1422. *First two authors contributed equally.

10) Bagni C. and Lapeyre B. (1998). “Gar1p binds to the small nucleolar RNAs snR10 AND snR30 in vitro through a novel RNA binding motif". J.Biol.Chem. 273, 18: 10868-10873.

11) Adinolfi, S., Bagni, C., Musco, G., Mazzarella, L and Pastore, A. (1999). "Dissecting FMR1, the protein responsible for fragile X syndrome, in its structural and functional domains". RNA 5, 1248-58.

12) Adinolfi S, Bagni C, Castiglione Morelli MA, Fraternali F, Musco G, Pastore A. (1999) "Novel RNA-binding motif: The KH module" Biopolymers 51:153-164

13) Mariottini P, ZH, Toivonen, JM., Bagni, C., Spelbrink, J.N., Amaldi, F and Jacobs, HT. (1999). "Expression of the gene for mitoribosomal protein S12 is controlled in human cells at the levels of transcription, RNA splicing and translation” J. Biol. Chem. 274, 31853-31862.

14) Bagni, C., Mannucci, L., Dotti, C. and Amaldi, F. (2000).“ Chemical stimulation of synaptosomes modulates a-CaMKII mRNA association to polysomes”.(J. Neurosci. 20, RC76 1-6.)

15) Cannata, SM., Bagni, C., Bernardini, S., Christen, B. and Filoni, S. (2001). "Nerve-independence of limb regeneration in larval Xenopus laevis is correlated to the level of FGF-2 mRNA expression in limb tissues. (Develop. Biol. 231, 436-446)

16) G. Pepe, B. Giusti, L. Evangelisti, M.C. Porciani, T. Brunelli, L. Giurlani, M. Attanasio, R. Fattori, C. Bagni, P. Comeglio, R. Abbate, G.F. Gensini. (2001).“Fibrillin-1 (FBN1) gene frameshift mutations in Marfan patients: genotype-phenotype correlations”. (Clin. Genet 59: 444-50).

17) Signori, E., Bagni, C., Primerano B., Papa, S., Rinaldi, M., Amaldi, F. and Fazio, V.M.(2001). "A somatic mutation in the 5' UTR of BRCA1 gene causes down-modulation of translation efficiency in an invasive sporadic breast cancer" (Oncogene 20 : 4596-600).

18) A. Schenck, B. Bardoni, A. Moro, C. Bagni and J-L Mandel (2001). “A highly conserved protein family interacting with the fragile X Mental Retardation Protein and displaying selective Interactions with the related proteins FXR1P and FXR2P” (Proc.Natl.Acad.Sci.98: 8844-9).

19) Bagni C, Gogos JA, Bray S, Kafatos FC and Hsu T. (2002). “The zinc finger protein CF2 functions downstream of MEF2 during muscle development in Drosophila”. Mech Dev. 117:265-268.

20) Primerano B, Tassone F, Hagerman P, Hagerman R, Amaldi F and Bagni C (2002). Reduced FMRP and increased FMR1 mRNA is proportionally associated with CGG repeat number and reflects a translational defect of the mRNA. RNA 8:1482-8.

21) Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta A., Surya R., Oostra, B., and Bagni, C. (2003). “The Fragile X Syndrome protein FMRP regulates the translation of specific mRNAs at the synspes via BC1 RNA” Cell 112, 317-327.

22) Zalfa F. and Bagni C. (2004) Molecular insights into mental retardation: multiple functions for the Fragile X Mental Retardation Protein? Curr. Issues in Mol. Biol. 6, 73-88.

23) Veneri M., Zalfa F. and Bagni C. (2004). “FMRP and its target RNAs: fishing for the specificity” . Neuroreport 15: 2447-2450.

24)Baldini P.M., De Vito P., Antenucci D., Vismara D., D’Aquilio F., Luly P., Zalfa F., Bagni C. and Di Nardo P. (2004) Atrial Natriuretic Peptide induces cell death in Human Hepatoblastoma (HepG2) through the involvenent of NADPH oxidase. Cell Dead and Differentiation; 11(S2):S210-S212.

25) Baldini P.M., De Vito P., Vismara D., Luly P., Bagni C., Zalfa F., Minieri M. and Di Nardo P. (2004). “Atrial natriuretic peptide effects on intracellular pH changes and ROS production in HepG2 cells: role of p38 MAPK and phospholipase D”. Mol. Cellul. Biochem, 15, 77-88.

26) Baldini, PM, De Vito, P, D'aquilio, F, Vismara, D, Zalfa, F, Bagni, C., Fiaccavento, R, Di Nardo, P.  (2005). "Role of atrial natriuretic peptide in the suppression of lysophosphatydic acid-induced rat aortic smooth muscle (RASM) cell growth". Mol. Cell. Biochem. 272, 19-28.

27) Pietrobono, R, Tabolacci, E, Zalfa, F, Zito, I, Terracciano, A, Moscato, U, Bagni, C, Oostra, B, Chiurazzi, P and Neri, G (2005). "Molecular dissection of the events leading to inactivation of the FMR1 gene" Hum. Mol. Gen. 14,  267-277.

28) Zalfa, F. and Bagni, C. (2005). "Another view of the role of FMRP in translational regulation". Cell. Mol. Life Sci. 62,  251-252.

29) Bagni, C., Greenough, W.T. (2005) "From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome" Nat. Rev. Neurosci. 5, 376-387.

30) Restivo, L., Passino, E., Sgobio, C.A., Ferrari, F., Oostra, B., Bagni, C. and Ammassari-Teule*, M. (2005). "Environmental manipulations restore behavioural and neuronal morphology abnormalities in a mouse model of Fragile X Mental Retardation Sindrome". Proc. Natl. Acad. Sci. U.S.A. 102, 11557-11562.

31)Baldini P.M., De Vito P., Vismara D., Bagni C., Zalfa F., Minieri M. and Di Nardo P. (2005) Atrial natriuretic peptide effect on intracellular pH changes and ROS production in HepG2 cells: role of p38 MAPK and phospholipase D. Cell. Physiol. Biochem; 15:77-88.

32)Baldini P.M., De Vito P., D’Aquilio F., Vismara D., Zalfa F., Bagni C., Fiaccavento A. and Di Nardo P. (2005) Role of atrial natriuretic peptide in the suppression of lysophosphatydic acid induced rat aortic smooth muscle (RASM) cell DNA synthesis. Mol. Cell. Biochem.; In press.

33) Zalfa, F., Adinolfi, S., Napoli, I., Kuhn-Holsken, E., Urlaub, H., Achsel, T., Pastore, A., Bagni, C. (2005). "FMRP binds specifically to the brain cytoplasmic RNAs BC1/BC200 via a novel RNA binding motif." J. Biol. Chem, (in press).