Objectif Mental retardation (MR) imposes a major medical and social-economical problem in our society. It is defined as a global reduction in cognitive and intellectual abilities, which manifests before the age of 18, and is estimated to affect 1-3% of the population. The causes of MR are extremely heterogeneous and include non-genetic factors as well as genetic changes that include chromosomal abnormalities and single-gene mutations. Great progress has been made over recent years towards the identification of MR-related genes, resulting in a list of approximately 400 genes. A largely remaining challenge, however, is to connect the genetic causes of MR to processes that establish and/or modify neuronal circuit function. Because learning deficit is a constant feature of those patients, it is tempting to attribute some of MR traits to alterations in synaptic functions. This research proposal is geared towards unravelling the molecular and cellular mechanisms underlying MR, focusing on the synaptic deficits of the disease. First, I will test the hypothesis that at the cellular level, MR proteins often impinge on synaptic function, and more specifically affect glutamate receptors expression and/or trafficking. Second, I will investigate in detail how genetic deficits found in MR lead to synaptic dysfunction in vivo. Several of the currently identified genes associated with MR code for regulators and effectors of the Rho GTPase family. These findings have led to the hypothesis that abnormal Rho GTPase signaling may be a prominent cause of MR. However, how alterations in Rho signaling result in changes in neuronal connectivity and/or plasticity that give rise to MR remain elusive. To gain insight into these pathways I will use a combination of molecular biology, optical imaging and physiology together with viral-mediated gene transfer methods to manipulate the molecular composition of single neurons in a spatial and temporal controlled manner. Champ scientifique medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesmolecular biology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Appel à propositions FP7-PEOPLE-2010-RG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur STICHTING RADBOUD UNIVERSITEIT Contribution de l’UE € 100 000,00 Adresse HOUTLAAN 4 6525 XZ Nijmegen Pays-Bas Voir sur la carte Région Oost-Nederland Gelderland Arnhem/Nijmegen Type d’activité Higher or Secondary Education Establishments Contact administratif Wim Van Oijen (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée