Obiettivo
"Protein misfolding and aggregation are associated with a wide range of severe, and so far incurable, neurological and systemic disorders, which include Alzheimer's and Parkinson's diseases, and type II diabetes. As these conditions are the consequence of the impairment of protein homeostasis, a variety of cellular natural defenses have evolved to eliminate protein aggregates as they form. In this application we are concerned with the problem of understanding the molecular basis of such defense mechanisms, by focusing on the specific case of the interaction between alpha-synuclein, a protein closely involved in Parkinson's disease, and Hsp70, a molecular chaperone with a variety of cellular functions, including the ability of recognising misfolded or aggregated proteins. We are going to address this problem using a wide arsenal of biophysical, biochemical and computational methods, including FRET and NMR spectroscopy, fluorescence methods, dynamic light scattering, transmission electron microscopy, isothermal titration calorimetry and molecular dynamics simulations. The outcome of this study will provide relevant structural information at atomic level on the binding modes of Hsp70 with diverse molecular forms of alpha-synuclein related to neurotoxicity. The results of this project are expected to increase our understanding of the molecular basis of the interactions between molecular chaperones and unstructured states of proteins, as well as to provide insights for the development of novel strategies for the rational design of therapeutic approaches against protein aggregation."
Campo scientifico
- natural sciencesphysical sciencesopticsmicroscopyelectron microscopy
- natural sciencescomputer and information sciencescomputational science
- natural sciencesphysical sciencesopticsspectroscopyabsorption spectroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein folding
- medical and health sciencesbasic medicineneurologyparkinson
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2010-IEF
Vedi altri progetti per questo bando
Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
CB2 1TN Cambridge
Regno Unito