Objective "Numerous pathological conditions, designated as misfolding diseases, involve conversion of specific proteins from their native, soluble state to highly ordered filamentous polymers. For many years these amyloid fibrils were considered to be inert end-products of the aggregation pathway, while the toxic properties were mainly attributed to soluble oligomeric intermediates. A recent study demonstrated that fully assembled amyloid fibrils induce cell death, and the observed toxic effects are inversely correlated with fibril length (Xue at al. J. Biol. Chem. 2009, 284, 34272-34282). The findings pointed out that membrane damage may be involved in the cell injury, however the detailed mechanism by which fibrils kill cells remains to be resolved.The proposed research is one of the first studies aiming to shed light on this important question through systematic investigation of fibril-membrane interactions. Specifically, screening distinct lipid components will be performed in order to allocate membrane binding to specific cellular targets. The impact of fibrillar dimensions on the membrane activity of the aggregates and their interactions with specific lipid components will be evaluated. Additional factors, such as pH and protein charge, will be investigated. The study will include several amyloidogenic proteins in order to assess the generic nature of the killing mechanism." Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencespolymer sciencesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipids 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) Topic(s) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2010-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator UNIVERSITY OF LEEDS Address Woodhouse lane LS2 9JT Leeds United Kingdom See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Administrative Contact Martin Hamilton (Mr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
