Objective
The aggregation of the amyloid-beta peptide (A-beta) into fibrils and successively in plaques is the main event in Alzheimer's disease. The A-beta originates from a membrane protein called amyloid-precursor protein. In healthy brain A-beta is present as soluble form and the predominant chains are formed by 40 or 42 amino acids. The oligomers of A-beta, rather then fully formed fibrils, are suspected to have nerotoxic properties. The transition metal zinc, copper, iron are present in amyloid plaques in abnormally elevated concentrations. It has been experimentally observed that Zn(II) and Cu(II) ions bind at A-beta(1-16) N-terminal sequence and influence aggregation behaviour: in particular Zn triggers and accelerates aggregation and Cu slows down or accelerates aggregation, dependently on conditions. Moreover A-beta bonded to Cu or Fe is able, probably by reducing oxygen, to produce reactive-oxygen species that are widely accepted to play a key role in most of neurodegenerative diseases. Afterwards there are several open questions about the metals/A-beta interaction: coordination chemistry, reactivity of these complexes, different behaviour of metals, peptide structure prone to aggregation, mechanisms of metal-induced aggregation. We propose to use computer simulations (both semiempirical and first principles) to understand the metal/A-beta system. Quantum mechanics methods (DFT) will be used to investigate the nature of metal bond and reactivity but statistical mechanics methods will be also necessary to obtain accessible peptide conformations in water. The Car-Parrinello method, that was successfully applied to similar systems in applicant's previous work, will be used. The project includes the acquisition of new relevant experiments on the kinetics of ROS production catalysed by Cu and Fe complexes of Abeta. Experiments will be based on the expertise of the host institution and specific training of the applicant is planned.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences physical sciences quantum physics
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences classical mechanics statistical mechanics
- natural sciences chemical sciences organic chemistry amines
- natural sciences mathematics applied mathematics mathematical model
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-IEF-2008
See other projects for this call
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
75794 PARIS
France
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.