PDF file: EURASNET Annual Report 2008

216 Aubeouf and Neugebauer willcollaborate to establishsplicing factor ChIP in MCF7cell lines. These breast cancercells are responsive toestradiol, which stimulatestranscription of cyclin D1,PS2 and other genes. Thiscellular model will allow usto test the splicing process ongene products made inresponse to hormones. Wewill establish stable cell lineswith integrated copies ofBACs expressing GFP-taggedversions of U1 70K, U2AF65,Prp8, CBP80 and members ofthe SR protein family, inorder to investigate theinterplay betweentranscription, cotranscriptionalspliceosomeassembly and AS outcome.(month 42)219 Bertrand and Neugebauer willcollaborate to determinewhether splicing of HIVnascent transcripts is cotranscriptional,using a modelgene comprising a split MS2reporter. ChIP of the MS2binding protein will indicatewhen and where along thegene splicing catalysis occurs.(month 42)220 Identification of novelmolecules based on luciferasemodel substrates for DMDexon 51 skipping and LMNAaberrant splicing. (month 42)221 Validation of the efficacy ofnovel synthesized compoundsin model mice for: Mo-MLV,HIV-1, DMD, Breast metasticcancer and HGPS (month 42)222 Validation of modified U7cassetes to correct SMNexpression in a mouse modelfor SMA (month 42)223 Development of clinicallyuseful drugs that direct thesplicing pathway: bothAntisense olinucleotides andsmall chemical molecules(month 42)13 Neugebauer O CO 4213 Neugebauer O CO 4214 Tazi O CO 4214 Tazi O CO 4214 Tazi O CO 4214 Tazi O CO 42235