Objectif Using Drosophilae way aim to a detailed and comprehensive knowledge of the physic-pathological role of Atrophies proteins, linked to dentatorubropallidoluysian atrophy (DRPLA).Neurodegenerative diseases due to polyglutamine expansion are a growing family of diseases affecting a consistent percentage of the population. They bear an enormous emotional impact for patients even before their onset and represent a considerable economic burden for society. DRPLA is caused by the expansion of a polyglutamine tract in the Atrophic-I protein. Recently, Drosophilae Atrophic has been identified, shown to encode a transcriptional co repressor and to be involved in several diverse processes from embryonic segmentation to eye development. The role Atrophic in the eye, the availability of several developmental assays, of a series of independently isolated mutations and other useful materials is unprecedented in the history of the use of Drosophilae to study neurodegeneration. We will engineer flies expressing the wild type and modified versions of Drosophilae Atrophic and the wild type and mutated human atrophic-I gene. We will then carry out genetic screens for modifiers of a rough eye phenotype and characterise the integrators for the role the may have in both the physiological and pathological functions of Atrophies. We will also use a genome-wide approach to monitor transcriptional regulation by Atrophies, eventual alterations due to polyglutamine expansions and their role in neurodegeneration. We expect to identify factors important for the normal regulations of the Atrophies, and that may be involved in signalling pathways that modify gene expression through Atrophies. In particular we aim to identify key factors for the role of Atrophies in DRPLA, to understand the peculiarity of the mutant proteins and determine the aberrant processes underling cellular pathology. Champ scientifique natural sciencesbiological sciencesneurobiologyhumanitieshistory and archaeologyhistorynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinepathology Mots‑clés Atrophin Drosophila eye neurodegeneration transcription Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Thème(s) MOBILITY-4.1 - Marie Curie European Reintegration Grants (ERG) Appel à propositions FP6-2002-MOBILITY-11 Voir d’autres projets de cet appel Régime de financement EIF - Marie Curie actions-Intra-European Fellowships Coordinateur FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR Contribution de l’UE Aucune donnée Adresse Via Olgettina 60 MILANO Italie Voir sur la carte Coût total Aucune donnée
