Cel 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. Dziedzina nauki medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesphysical sciencesthermodynamicsnatural sciencesphysical sciencesopticsspectroscopyemission spectroscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencesanalytical chemistrycalorimetry Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2011-CIG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-CIG - Support for training and career development of researcher (CIG) Koordynator VILNIAUS UNIVERSITETAS Wkład UE € 100 000,00 Adres UNIVERSITETO G. 3 01513 Vilnius Litwa Zobacz na mapie Region Lietuva Sostinės regionas Vilniaus apskritis Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Daumantas Matulis (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
