Obiettivo Small soluble protein aggregates play a key role in the onset and spreading of Alzheimer’s and Parkinson’s diseases. However, which oligomers are present in human disease and which are toxic remains unknown because ultrasensitive methods do not exist to detect and characterise the low concentration of oligomers, which are highly heterogeneous in size and structure. To address this problem we will develop fluorescence based methods to detect and characterise individual oligomers to measure the oligomer size, structure, proteinase K resistance, seeding capability and composition. We will also develop methods to enrich these oligomers so we can use mass spectrometry to determine post translational modifications and recover the oligomers to directly test their cytotoxicity and mechanism of damage. The capability to characterise these oligomers at this unprecedented level of detail will represent a major advance in the field. These methods will then be applied to stem cell models of Alzheimer’s disease and Parkinson’s disease and then clinical samples of CSF from patients. These experiments will determine how the number, composition or structure of the oligomers changes in the disease and if this results in increased cytotoxicity. Clinical samples of CSF from patients with genetic mutations will be used to determine if detectable changes in the oligomers occur early in the disease and samples of brain tissue used to determine the changes in oligomers during the spreading of the disease.By the end of the project we will have determined which oligomers play major roles in the onset and spreading of Alzheimer’s and Parkinson’s disease in humans, providing targets for therapies, and tested if the detection and characterisation of these oligomers can be used for early diagnosis of the disease. Campo scientifico medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesbasic medicineimmunologyimmunotherapy Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-ADG-2014 - ERC Advanced Grant Invito a presentare proposte ERC-2014-ADG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contribution nette de l'UE € 2 499 551,00 Indirizzo TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Regno Unito Mostra sulla mappa Regione East of England East Anglia Cambridgeshire CC Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 499 551,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Regno Unito Contribution nette de l'UE € 2 499 551,00 Indirizzo TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Mostra sulla mappa Regione East of England East Anglia Cambridgeshire CC Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 499 551,00
