Description du projet
Vision moléculaire de la physiopathologie de la maladie de Parkinson
La maladie de Parkinson est une maladie neurodégénérative qui se manifeste par des tremblements et une perte progressive du mouvement. La caractéristique de cette maladie est la formation d’agrégats de la protéine alpha-synucléine dans des corps d’inclusion appelés corps de Lewy. Le projet SYN-CHARGE, financé par l’UE, vise à mettre au jour le mécanisme à l’origine de la toxicité de ces agrégats de protéines. Les chercheurs étudieront l’interaction entre l’alpha-synucléine et d’autres protéines neuronales, afin de mieux appréhender les bases de la physiopathologie de la maladie de Parkinson. Les résultats pourraient déboucher sur de nouvelles cibles moléculaires pour la conception de nouvelles interventions thérapeutiques.
Objectif
Alpha-synuclein (aSN) is an intrinsically disordered protein (IDP) expressed by neurons, and well-known to aggregate in so-called Lewy bodies (LB) that are a hallmark of Parkinson’s disease (PD) and other LB disorders. Despite extensive research, the mechanisms underlying its toxicity in these disorders still remains to be understood. In this project, I will determine whether aSN can interact with other disordered proteins in a novel, mean-field type interaction, focusing on the disordered loop of the neuronal plasma membrane Ca2+ ATPase (PMCA). I will study this using biophysical techniques, in particular NMR, ITC and SAXS/SANS. This project will improve the understanding of aSN and its interactions and has the potential to pave the way for new discoveries, especially in drug design. I will gain important experience in project design and management, a research network in Europe, and take a significant step towards independence. I will undertake this project at the University of Copenhagen in the research group of Professor Birthe B. Kragelund, an expert in the field of IDP research. The Kragelund group has recently joined the BRAINSTRUC Consortium: a group of researchers working on the structural characterization of neuronal proteins. Thus, they required a postdoctoral researcher with a strong background in neuroscience and structural biology. I was uniquely qualified to take this position as I have been working on neurodegenerative proteins for several years and structurally characterized the IDP associated with Huntington’s disease. Professor Kragelund has experience supervising productive postdoctoral researchers, an extensive European network, and has access to the state-of-the-art facilities necessary to complete this project. I have recently acquired preliminary data to indicate that the two proteins (aSN and PMCA) interact directly. This project has the potential to change how we understand proteins associated with neurodegeneration and their interactions.
Champ scientifique
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
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Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1165 Kobenhavn
Danemark