Molecular cellular and metabolic neuronal pathways of Fragile X Syndrome
Mental retardation (MR) is a major cause of serious handicap, as well as an important medical and social issue, affecting 2-3% of the population. The Fragile X Syndrome (FXS) is the most frequent hereditary cause of MR affecting 1...
ver más
¿Tienes un proyecto y buscas un partner? Gracias a nuestro motor inteligente podemos recomendarte los mejores socios y ponerte en contacto con ellos. Te lo explicamos en este video
Proyectos interesantes
Synapses FXS
Characterization of the molecular components of synapses in...
220K€
Cerrado
PDC2022-133775-I00
UNA NUEVA ESTRATEGIA TERAPEUTICA PARA EL SINDROME DE X FRAGI...
132K€
Cerrado
PID2019-106608RB-I00
PERFIL DE INTERACCION DE NCS-1 ( NEURONAL CALCIUM SENSOR-1)...
119K€
Cerrado
FXSdev
Cortico-striatal circuit assembly in Fragile X Syndrome
189K€
Cerrado
PID2020-114030RB-I00
ESTRATEGIAS DE RESCATE DE LA PLASTICIDAD SINAPTICA Y FUNCION...
250K€
Cerrado
NeuroStemX
In vitro model of Fragile X Syndrome using naïve iPSCs
183K€
Cerrado
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Mental retardation (MR) is a major cause of serious handicap, as well as an important medical and social issue, affecting 2-3% of the population. The Fragile X Syndrome (FXS) is the most frequent hereditary cause of MR affecting 1/4000 males and 1/7000 females, due to the inactivation of the X-linked Fragile X Mental Retardation 1 gene (FMR1). In FXS patients and the Fmr1 knock-out mouse, the lack of the gene product, the RNA-binding protein FMRP, induces behavioural and cognitive abnormalities, coupled to alterations of synaptic plasticity and morphology, most probably due to alterations of the transport and localized synaptic translation of specific mRNA targets of FMRP. To better understand the role played by FMRP in this processes, I propose to first systematically identify the mRNA specifically targeted by FMRP in RNA granules, the mRNP particles that transport mRNA towards the synapse, using a transcriptomic approach. In addition, I will identify the protein partners of FMRP in the neuronal RNA granules, using mass-spec analysis of the proteins coimmunoprecipitated with FMRP in biochemical preparations of RNA granules. Finally, I will use proton nuclear magnetic resonance spectroscopy (1H NMR) and multivariate pattern recognition to characterize the neurochemical perturbations and define a metabolic signature of FXS in Fmr1 KO mice, that will further enable a pharmaco-metabonomic study of FXS treatment efficacy. This project will essentially be developed at the IPMC, in Dr Bardoni's laboratory (Aim 1 and 2) but also in close collaboration with a Canadian laboratory (Prof. Khandjian, Univ. Laval, Québec) and with a French laboratory (Aim 3, Dr Dumas, ENS Lyon) and. By integrating the molecular and metabolic data obtained following this trans-disciplinary approach, I expect to contribute significantly to the understanding of the neuronal alterations induced by the absence of FMRP in FXS patients, and to validate therapeutical molecules.