PDF file: EURASNET Annual Report 2008

properties of the human TDP-43 protein itself by performing, in collaboration with other groups, CLIP analysis toidentify the in vivo RNA binding targets of TDP-43 in neuronal cells. Finally, the group will also express severalTDP-43 recombinant proteins carrying the most representative amino acids substitutions associated with diseaseto better understand how these changes might affect the basic molecular properties of the wild-type protein.330 GROUP 11 (BINDEREIF) will continue our collaboration with the Sprecher’s group in Israel, characterizingthe role of RBM28 in human disease, and exchanging materials (patient cell lines, antibodies) as well as specialexpertise (by month 54)In addition, a new collaboration developed recently with the immunology group of Hans-Martin Jaeck (Divisionof Molecular Immunology, Nikolaus-Fiebiger-Center for Molecular Medicine, Klinikum of the University ofErlangen), with the aim to characterize the role of hnRNP LL in different cell types of the immune system (month54).331 GROUP 25 (STEVENIN) will continue to characterize further the alternate binding of splicing regulators tothe region of LMNA transcripts, which is mutated in HGP Progeria patient, with Partner 12a and 12c.They will also analyze, in collaboration with A. Martins et M. Tosi (INSERM, Rouen, France), the involvementof factors which are implicated in splicing of wild-type MSH2 exon 5 and MLH1 exon 10 versus mutant exonsfrom HNPCC patients (hereditary nonpolyposis colorectal cancer).332 GROUP 26 (AUBOEUF) is currently working towards what could be a new deliverable for month 42 on“Genome wide analysis of alternative splicing using Affymetrix Exon Arrays on microdissected tumor and normaltissue specimens”.333 GROUP 27 (GABELLINI) will:1) focus on validation of splicing-sensitive microarrays results by performing RT-PCR using RNA extracted from:a) muscle of FRG1 and WT mice different from the one used to perform the microarrays;b) muscle of mdx mice (mouse model of Duchenne muscular dystrophy) to determine which changes are due tosecondary effects of the dystrophic process;c) C2C12 muscle cells over-expressing FRG1 and controls to determine which changes are directly due to FRG1over-expression;d) muscle of healthy subjects, patients affected by FSHD and patients affected by other muscular dystrophies todetermine which changes are specific of FSHD;2) search for conserved binding sites around the exon/intron regions of pre-mRNA affected by FRG1 overexpression;3) determine which are the GO categories preferentially affected by FRG1 over-expression;4) perform functional studies on selected FRG1 pre-mRNA targets;5) evaluate safety and efficacy of shRNAs specific for FRG1 systemically delivered by rAAVs as a possibletherapeutic approach for FSHD.266