Dynamic proteomic maps of stem cell derived neurons as a mechanistic discovery p...
Dynamic proteomic maps of stem cell derived neurons as a mechanistic discovery pipeline for rare neurological disease
Rare diseases are a major unmet medical need, as is the definition of the relevant disease mechanisms. Many rare diseases affect the nervous system. These are challenging to treat, and mechanistic studies are difficult due to the...
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
FoldTox
Understanding the cytotoxicity of aberrantly folded proteins...
45K€
Cerrado
PROTEOSTASIS
Cell type specific modulation of protein homeostasis in heal...
100K€
Cerrado
RYC2021-030946-I
Systems biology and clinical proteomics for the study of neu...
236K€
Cerrado
NOVEL TOOLS IN PD
Novel tools for real time monitoring and quantification of p...
1M€
Cerrado
EUROSPIN
European Consortium on Synaptic Protein Networks in Neurolog...
16M€
Cerrado
PTQ-09-02-02148
EXPLORACIÓN DE NUEVAS DIANAS ENFERMEDADES NEURODEGENERATIVAS...
69K€
Cerrado
Información proyecto RARE MAPS
Duración del proyecto: 35 meses
Fecha Inicio: 2020-02-24
Fecha Fin: 2023-01-31
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Rare diseases are a major unmet medical need, as is the definition of the relevant disease mechanisms. Many rare diseases affect the nervous system. These are challenging to treat, and mechanistic studies are difficult due to the inaccessibility of patient tissue. Global proteomic studies have provided insight into whole tissue or cell changes in protein abundance but lose information on protein subcellular localisation, which is important because defects in protein trafficking are implicated in many neurological disorders. In ‘RARE MAPS’ I propose an unbiased mechanistic discovery pipeline combining human induced pluripotent stem cells (hiPSCs) with advanced spatial proteomics. I will use a method developed by Dr. Borner called ‘dynamic organellar maps’, which provides quantitative protein subcellular localisation information at the whole proteome level. Used comparatively, it can detect changes in protein localisation due to a perturbation, allowing unbiased screening for phenotypic changes. To develop this workflow, I will apply it to the rare neurodegenerative disorder AP-4 deficiency syndrome. AP-4 knockout hiPSCs will be differentiated into cortical neurons and maps will be made of intermediate cortical stem cells and mature cortical neurons. Comparison to control cells will enable the detection of changes to protein localisation and abundance. I will also apply the maps to brain tissue from an AP-4 deficient mouse model to detect protein mislocalisation in vivo. I will then use CRISPR/Cas9 technology to investigate the role of novel and known AP-4-associated proteins in neuronal autophagy and axonal health. This project will demonstrate the utility of dynamic organellar maps to reveal molecular mechanisms of rare neurological disorders as well as provide new insights into the pathogenesis of AP-4 deficiency and the role of protein trafficking and autophagy in the axon.