Objective
The proteins Tau and α-synuclein are causative agents of several neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. In physiological conditions these neurotoxic proteins adopt a disordered conformation but undergo conformational transitions leading to their aggregation and amyloid fibril formation under neuronal stress. ATP-driven molecular chaperones of the heat-shock protein (Hsp) family have been postulated to play a critical role in inhibiting the gain-of-toxic function of these proteins. However, little is known about the binding and activation mechanism of neurotoxic proteins, and of disordered proteins in general, induced by Hsps. Given the dynamic and unstable nature of these interactions and activation cycles, NMR spectroscopy is ideally suited to obtain insight into the nature of these interactions. In the attached application I propose to obtain - by means of novel artful NMR experimental designs, complemented with extensive biochemical and biophysical characterization - a detailed model of the aggregation-prone fragment of Tau bound to the two different allosteric conformations of Hsp70. This will for the first time shed light onto the still unsolved conformational changes in a client protein motivated by the chaperone mode of action. Moreover, I will study several disease-related Tau mutants, the role of cochaperones in this cycle, as well as the effect of inhibitors to better understand the mechanism of Hsp-substrate interaction. In addition, the detailed structural information that will be obtained in this project will provide the basis to chemically optimize available inhibitors and test their cellular effect in the last phase of the project. The opportunity to carry out this ambitious project represents a significant step forward for my future independent career, being deeply involved in state-of-the-art methodological and biological tutoring in a scientific environment that is tightly connected to the industry sector.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
- medical and health sciences basic medicine neurology parkinson
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IEF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
53127 Bonn
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.