Cellular and molecular studies of synaptic plasticity in the context of the Fragile X Syndrome
One of the big tasks in neurobiology is to understand how a neuronal cell can store previous experience and change its output accordingly: the basis of learning and memory. A crucial contribution comes from regulated local protein synthesis in the dendrites and axons of the neuronal cell.
To understand how this process contributes to learning and memory processes, three broad questions have to be addressed:
- How are the necessary components of the protein synthesis machinery transported to the dendrites/axons?
- What triggers local protein synthesis?
- What downstream processes are affected by regulated translation?
My lab has extensively studied the molecular basis of the Fragile X Syndrome (FXS), which is caused by the absence of the Fragile X Mental Retardation Protein, FMRP.
FMRP is implicated in mRNA metabolism at synapses, and the study of the protein and of its mRNA offers a major inroad into the understanding of the learning and memory processes. We will use this approach further to obtain a complete understanding of the regulation of synaptic protein synthesis. Finally, Autistic Spectrum Disorder is linked to the Fragile X Syndrome; in fact, FXS is the monogenic Syndrome with the highest incidence of Autism.
Both the Fragile X Syndrome and Autism are still without an effective cure. We will therefore use the knowledge obtained from these lines of research to identify, in collaboration with clinical researchers, possible pharmacological approaches and strategies.
BC1-FMRP interaction is modulated by 2'-O-methylation: RNA-binding activity of the tudor domain and translational regulation at synapsesLacoux C, Di Marino D, Pilo Boyl P, Zalfa F, Yan B, Ciotti M, Falconi M, Urlaub H, Achsel T, Mougin A, Caizergues-Ferrer M, Bagni CNUCLEIC ACIDS RESEARCH, 40, 4086-4096, 2012 Differential usage of transcriptional start sites and polyadenylation sites in FMR1 premutation allelesTassone F, De Rubeis S, Carosi C, La Fata G, Serpa G, Raske C, Willemsen R, Hagerman P, Bagni CNUCLEIC ACIDS RESEARCH, 39, 6172-6185, 2011
19/01/2011 - This 2011 EMBO Conference Series will cover recent advances in the field of regulation of mRNA localization and localized translation.
Ph.D.: University of Rome, Italy, 1992
Post-doc.: CNRS, France, 1991-93
Post-doc.: Harvard University, Cambridge, USA, 1993-94
Post-doc.: EMBL, Germany, '94-'96
Associate Professor, University of Rome ”Tor Vergata”, Italy, since 2002
EMBO member since 2011
VIB Group leader since 2008