Descripción del proyecto
Información molecular de la fisiopatología de la enfermedad de Parkinson
La enfermedad de Parkinson es un trastorno neurodegenerativo asociado con temblores y una pérdida progresiva de la movilidad. La característica distintiva de la enfermedad es la formación de agregados de la proteína alfa-sinucleína en cuerpos de inclusión conocidos como cuerpos de Lewy. El proyecto financiado con fondos europeos SYN-CHARGE pretende definir el mecanismo que subyace a la toxicidad de estos agregados de proteínas. Los investigadores estudiarán la interacción de la alfa-sinucleína con otras proteínas neuronales y ofrecerán información fundamental sobre la fisiopatología de la enfermedad de Parkinson. Los resultados podrían conducir a nuevas dianas moleculares para el diseño de intervenciones terapéuticas novedosas.
Objetivo
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.
Ámbito científico
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
1165 Kobenhavn
Dinamarca