Objectif Protein fibrillation is an important research topic in different scientific fields. For example, increased knowledge on protein fibrillation may clarify different aspects related to pathologies like Alzheimer's and Parkinson's diseases, which are characterized by the build-up of amyloid fibrils in the involved tissues. An important aspect of fibril formation is the ability of fibril itself to catalyze the fibrillation process, known as secondary nucleation, with the fibril surface playing a still poorly understood role in this mechanism. The present proposal aims to investigate aspects of macroscopic fibril polymorphism in relation to the molecular structure of the fibrils and the molecular mechanism of aggregate growth. The focus will be on the surface properties of the fibrils and their role in determining both the evolution of the aggregate growth and the 3D arrangement. Fibril formation will be studied in vitro for two different systems: insulin and alpha synuclein (aSN). The temporal features of the aggregation process will be studied in different experimental conditions using an approach based on amyloid sensitive probes and dynamic light scattering. A morphological investigation on the macroscopic scale of the occurring species will be performed by means of imaging techniques (atomic force and optical microscopy) and the structural details of these species (both intermediate and mature aggregates) will be investigated by small angle X-ray scattering and X-ray fibre diffraction. Surface structural details will be investigated by a novel approach based on a combined use of SAXS and ultrasonic resonator technology, able to provide quantitative information on the compressibility of the solvent around the aggregate. The catalytic propensity of species with different surface properties will be quantified by fluorescence spectroscopy during seeding experiments, and visualized by confocal microscopy. Champ scientifique medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesphysical sciencesopticsspectroscopyemission spectroscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyconfocal microscopymedical and health sciencesbasic medicineneurologyparkinson 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-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Appel à propositions FP7-PEOPLE-2011-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur KOBENHAVNS UNIVERSITET Contribution de l’UE € 228 082,20 Adresse NORREGADE 10 1165 Kobenhavn Danemark Voir sur la carte Région Danmark Hovedstaden Byen København Type d’activité Higher or Secondary Education Establishments Contact administratif Ivan Kristoffersen (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
