Objective
Several neurodegenerative and systemic amyloid diseases are putatively caused by the formation of insoluble protein fibrils, which accumulate in human tissues and interfere with normal organ function. The amylome is the set of proteins that are capable of forming amyloid-like fibrils, as consequence of the self-aggregation of some segments.
The familial amyloidosis or FAP is a slowly progressive condition characterized by the buildup of abnormal deposits of transthyretin (TTR) in the body's organs. Most patients with FAP have early and severe impairment of the autonomious nervous system and also visual deterioration. A variant of TTR, presenting the D38A mutation, was detected in patients suffering from amyloidosis. Analysis performed by Eisenberg's team showed that the aspartic acid 38 is likely to be within a non self-aggregating segment in the native protein (ADDTWE). However, when this segment carries the mutation (AADTWE), it turns into a self-associating segment (not published). We hypothesize that this segment is the cause of the fibrillation of transthyretin for the D38A mutation and that disrupting packing of the fibril spine can hinder fibrillation.
The goal of this proposal is the structure-based design of a blocker of aggregation of amyloid fibers of the segment AADTWE in the mutant TTR[D38A]. We will develop two different strategies for designing putative blockers of the aggregation of TTR: the structure-based design of an all D-peptide inhibitor and the construct of a chimeric protein between aggregation-inhibitor HET-S globular domain and the self-aggregating segment AADTWE. We will have to check the established inhibition model by X-ray crystallography and NMR techniques. Finally, inhibitors can be purchased commercially for synthesis of the designed fibril blockers.
This project can be considered as a key in biomedical improvement, especially in neurodegenerative diseases, because it could bring us a way to stop the development of these illnesses.
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 biological sciences neurobiology
- engineering and technology materials engineering fibers
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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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-2011-IOF
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
8092 Zuerich
Switzerland
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.