Obiettivo Increasing number of peptides and proteins are found to form ordered fibrillar aggregates under certain conditions. Amyloid-like fibrils are associated with a number of diseases, ranging from neurodegenerative diseases to systemic amyloidoses. Current studies have shown the ability of (-)-Epigallocatechin 3-Gallate (EGCG) to inhibit fibril formation and even to dissociate fibrils. Nevertheless, some EGCG-resistant structures were also reported. To evaluate EGCG as a possible drug candidate against amyloid diseases, extensive studies of protein aggregation in presence of the ligand is necessary.The proposed research will construct a comprehensive map of EGCG-insulin amyloid interactions.1. At varying conditions insulin forms fibrils via different pathways. The impact of EGCG on the pathway of aggregation will be studied.2. At varying conditions insulin aggregates into distinct amyloid structures, mimicking prion-like ‘strains’. The impact of EGCG on insulin ‘strains’ will be studied.3. Insulin fibrils can elongate at conditions not favorable for de novo fibril formation. The impact of EGCG on fibril elongation (mimicking prion-like infectivity) will be studied.Isothermal titration calorimetry (ITC) will be used to study insulin-EGCG binding. Also ITC will be used to determine thermodynamic parameters of fibril elongation. Differential scanning and pressure perturbation calorimetry (DSC and PPC), ultrasound velocimetry, densitometry and fluorescence spectroscopy will give insight into kinetics and thermodynamics of insulin aggregation in presence of EGCG at different conditions. Fourier-transform infrared (FTIR) spectroscopy will be used to monitor changes in secondary structure, and atomic force microscopy (AFM) will show the morphology of aggregates. Campo scientifico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesphysical sciencesthermodynamicsnatural sciencesphysical sciencesopticsspectroscopyemission spectroscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencesanalytical chemistrycalorimetry Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Invito a presentare proposte FP7-PEOPLE-2011-CIG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-CIG - Support for training and career development of researcher (CIG) Coordinatore VILNIAUS UNIVERSITETAS Contributo UE € 100 000,00 Indirizzo UNIVERSITETO G. 3 01513 Vilnius Lituania Mostra sulla mappa Regione Lietuva Sostinės regionas Vilniaus apskritis Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Daumantas Matulis (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
