PDF file: EURASNET Annual Report 2008

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ChemicalsEnzymesLaboratory supplies2160 Euro3555 Euro2439 EuroTravel 7289.65Personnel: The personnel were members of the laboratory who carried out the research involved inwork packages 8 and 13. The personnel include both research associates as well as technical staff. Theresearch associates carried out the experiments where as technical staff carried out routine laboratorysupport such as glassware washing, preparing reagents etc.Consumables: Consumables includes all reagents required for the experiments including expensivemolecular biology reagents such as reverse transcriptase and RNAse inhibitors. Also included are kitsfor production of probes and RNA extraction. Other supplies include routine laboratory disposablessuch as gloves , plasticware test tubes etc.Travel: Travel was to attend the <strong>EURASNET</strong> meetings including the meeting in Edinburgh .183
Participant 25 - James SteveninWP 7. We have shown that the last exon of SC35 pre-mRNA is responsible for a negative retro-controlof SC35 production at the splicing step. The regulation occurs at the level of alternative splicing, theinvolvement of 2 kinds of trans-acting factors with opposite activities (SC35 as a positive factor andhnRNP H and TDp43 as negative factors) allowing the production of various mRNA isoforms ofdifferent stabilities. In collaboration with the group 12c, (C. Branlant), we also determinedexperimentally the secondary structure of the evolutionary conserved regulatory region in this SC35terminal exon. This opened the possibility to identify the binding sites for regulatory proteins (seedeliverable 166).WP 14. We had previously validated specific extracts from human cells overexpresssing various SR orTra2 proteins to analyse splicing of LMNA transcripts, in collaboration with Jamal Tazi’s group. Wehave used now such extracts to reveal some RNA-proteins interactions with specific regions of LMNAgene, under ithe wild type or mutated formsWP 12. We have further characterized the alternate binding of splicing regulators to the region ofLMNA transcripts, which is mutated in HGP Progeria patient, leading to the use of a cryptic 5' splicesite within exon 11. Using a slightly different approach, they have confirmed results obtained byPartner 12c (Christiane Branlant), especially the disruption of an ASF/SF2 binding site in mutanttranscripts. Using a specific in vitro assay developed in the lab to monitor LMNA exon 11 splicing,they will now analyse whether this factor may or not repress the use of the cryptic site in wild-typetranscripts.In collaboration with A. Martins et M. Tosi (INSERM, Rouen, France), we have also looked for factorsthat bind differentially to wild-type MSH2 exon 5 and MLH1 exon 10 versus mutant exons fromHNPCC patients (hereditary nonpolyposis colorectal cancer). Several factors (SR and hnRNP proteins)have been found and our collaborators will now study their involvement using in vitro and in vivominigene assays.b) Major cost items with justificationMajor cost itemsParticipant 1A Type of expenditure Budget total costspersonnel 45573.68consumables 0training 0equipment 0travel 2027.86= total direct costs 47499.68+ overhead 8549.94Adjustment on previous -3725.84= total eligible costs 52323.78• ResearchPersonnelNatacha Dreumont [WP 7,12,14 ] 1470 hours 45573.68 EuroTravel (2027.86 Euros)Stevenin James : 20-23.01.<strong>2008</strong> Mission to Eurasnet Meeting, Berlin, GermanyStevenin James : 21-25.05.08 Mission to “International Eurasnet Alternative SplicingConference” Krakow, Poland, France (Inscription Flight, Parking etc)Bourgeois Cyril : 21-25.05.08 Mission to “International Eurasnet AlternativeSplicing Conference” Krakow, Poland, France (Inscription Flight, Parking, etc)184
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TABLE OF CONTENTSA. PERIODIC ACTIVI
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1 PUBLISHABLE EXECUTIVE SUMMARY EUR
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Dr. Davide Gabellini(28) Swiss Inst
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WP7 Molecular characterization of s
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To identify protein-protein interac
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expressed in a particular tissue. T
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Duchenne muscular dystrophy (DMD).
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WP21 Reachout to the broader RNA co
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4.1 TABLE OF MILESTONES JPA MONTH 2
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Numerous plasmids, constructs, extr
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collaboration between EURASNET and
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5.1 WORK PACKAGE REPORTSWork Packag
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• Ongoing regular addition of new
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Work Package 4 The Alternative Spli
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Work Package 6 In silico approaches
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alternative splicing.162 Compare sp
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33 Agreement on pre-mRNA substrates
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its numerous binding sites on both
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Work Package 8 Genome-wide Analyses
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173 Further development of data ana
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Problems and explanations for delay
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eveal that there is a dramatic chan
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Work Package 10 Post-translational
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mutational analysis that led to the
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Isolation of an active step I splic
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FBP11 and 21 with these sequences.
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Similarly to what observed for SF2/
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prp45-113 mutant, which is compatib
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cell lines. In contrast in the pres
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genes with roles in the development
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Structural analyses of several RRMs
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Work Package 17 Staff Exchange and
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Barralle's lab, Krämer is acting a
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alternative splicing) and higher ed
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Student Symposium “Decision Makin
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variation and suitability for use w
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Following feedback from members we
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Invited seminars: In addition to me
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Publications 2008Author Title Publi
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Author Title Publication EURASNET P
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Minutes of the General Assembly dec
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241 Evaluate available careerdevelo
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156 The EURASNET memberStamm publis
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y coarse-grained foldingsimulation.
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overexpressor and mutant lines(mont
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machinery with particularrespect to
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alternative splicing, using theEDI
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contemporary findings withinthe EUR
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Licht K, Medenbach J, Lührmann R,K
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9 TABULAR OVERVIEW OF MAJOR COST IT
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total costs * 18.891,12 52778.60 41
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other (the rest) 48,57 0 56.539,43t
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travel 6.964,91overhead 3.081,07oth
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Participant 1A Type of expenditure
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Participant 1B - Karla Neugebauera)
Page 134 and 135: Participant 2 - Juan Valcarcela) Wo
Page 136 and 137: Participant 3 - Stefan Stamma) Work
Page 138 and 139: Participant 4 - Göran Akusjärvia)
Page 140 and 141: Participant 5A/B - Peer Bork/Rolf A
Page 142 and 143: Major cost items• ResearchPersonn
Page 144 and 145: Participant 7 - Francisco Barallea)
Page 146 and 147: Francisco Baralle gave a talk to a
Page 148 and 149: alternative splicing on human disea
Page 150 and 151: J. Beggs has had frequent contact w
Page 156 and 157: Participant 12A - Jamal Tazia) Work
Page 158 and 159: Participant 12B - Bertrand Séraphi
Page 160 and 161: Participant 12C - Christiane Branla
Page 162 and 163: Participant 12D - Edouard Bertranda
Page 164 and 165: Participant 13 - Daniel Schümperli
Page 166 and 167: Participant 14 - John W. S. Browna)
Page 168 and 169: Participant 15 - Javier F. Cáceres
Page 170 and 171: • ResearchPersonnelName WP Person
Page 172 and 173: MiscellaneousOligonucleotidesUse of
Page 174 and 175: Major cost items• ResearchConsuma
Page 178 and 179: Participant 21 - Angela Krämera) W
Page 180 and 181: Participant 22 - Angus Lamonda) Wor
Page 182 and 183: Participant 23 - Chris Smitha) Work
Page 186 and 187: Participant 26 - Didier Auboeufa) W
Page 188 and 189: tool for the molecular analysis of
Page 190 and 191: Participant 29 - Frédéric Allaina
Page 192 and 193: protein and instead possesses the d
Page 194 and 195: + overhead 4.730= total eligible co
Page 196 and 197: Claudia Tamaro (PhD) has begun work
Page 198 and 199: ETHZIIMCBUPFSOTON-HGDTOTALJoint Pro
Page 200 and 201: Direct eligible costs 53.240,48 0,0
Page 202 and 203: Direct eligible costs 18.720,07 0,0
Page 204 and 205: 13 REPORT ON THE DISTRIBUTION OF TH
Page 206 and 207: Report on the Distribution of the C
Page 208 and 209: For most work packages here follows
Page 210 and 211: pathways (eg, Reactome ).While PAND
Page 212 and 213: The possible dependence of the effe
Page 214 and 215: In some treatments or mutants, simi
Page 216 and 217: Work Package 12: Mis-splicing and D
Page 218 and 219: acid. Furthermore, using antibodies
Page 220 and 221: At the 2007 annual meeting in Ile d
Page 222 and 223: Partner 13 has extensively studied
Page 224 and 225: inhibitors/modulators of RNA splici
Page 226 and 227: 18 MONTH JPA: WORKPACKAGE TIMECOURS
Page 228 and 229: 15.3 GRAPHICAL PRESENTATION OF WORK
Page 230 and 231: 15.4 TABLE OF MILESTONES (MONTH 37-
Page 232 and 233: 156 The EURASNET memberStamm publis
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194 Bertrand will analyze indetail
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216 Aubeouf and Neugebauer willcoll
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238 Establishing joint PhDcommittee
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283 A unified browser for allknown
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296 Group 12a (Branlant) willuse th
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315 Lamond will use a FLIM-FRET bas
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329 GROUP 7 (F. BARALLE)will contin
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333 GROUP 27 (GABELLINI)will:1) foc
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345 Schümperli’s group isplannin
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366 Quarterly network e-mail atmont
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2. Sharing Resources, Technology an
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5. Ensuring DurabilityWorkpackage d
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7. Molecular Characterization of Sp
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8. Genome-wide Analyses of Splicing
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9. Complexity of Spliceosomal Prote
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202 Srebrow will investigate the ro
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12. Mis-splicing and DiseaseWorkpac
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13. Co-transcriptional Mechanisms o
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14. Chemical Biology and Therapeuti
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15. Development of Enabling Technol
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269 IFMs in 20091. “Alternative a
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18. Career DevelopmentWorkpackage d
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20. SMEs and Technology TransferWor
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21. Reachout to the Broader RNA Com
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15.7 WORK PACKAGE LIST (MONTHS 37-5
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ETHZIIMCBUPFSOTON-HGDTOTALJoint Pro
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AMU 5 29 8 42UAAR 5 145 16 1665 29
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Joint Programme of Activities RESEA
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60 month period 18 month periodRequ
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Integration1. Young Investigator Pr
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UCAM-DBIOC 2350,000x1/3 € 50,000x
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the management team. Audit costs ar
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