Objective
Aberrant folding and aggregation of soluble proteins into amyloid-like deposits has been associated to more than 20 known human disorders, including Alzheimer's disease, spongiform encephalopathies and type II diabetes. Recent research has indicated that the early oligomers present prior to amyloid fibril formation represent the most dangerous species to the cell and that their specific conformational properties determine their toxicity. It has been therefore realised that the structural characterization of these oligomers represents a crucial step in the development of treatments for diseases associated with abnormal protein aggregation.
This objective, however, presents formidable challenges, due to the transient lifetime and the heterogeneous nature of such oligomeric species. In this fellowship application we propose to exploit the ability of specific antibodies to bind the early oligomeric aggregates of lysozyme in order to characterise structurally the initial steps of its amyoidogenic pathways. The camel single domain antibody, cAb-HUL5, significantly inhibits fibril formation in lysozyme by stabilising dimers or early oligomers, thus effectively preventing them from being incorporated into higher order oligomers and fibrils. These antibody-bound dimers will be characterised by advanced NMR methods and the structural information acquired in this way will subsequently be used in structure calculations.
We will thus be able to obtain for the first time an ensemble of structures representing the conformations populated by the antibody-bound dimeric state of lysozyme. The results of this project will clarify important fundamental aspects of the early stages of the processes of fibril formation and aggregation of proteins, and offer a basis for the development of therapeutic strategies for several debilitating diseases associated with protein aggregation.
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.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
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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.
FP6-2005-MOBILITY-5
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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
CAMBRIDGE
United Kingdom
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.