Objective
Protein misfolding and aggregation into amyloid fibrils is a hallmark of serious diseases such as Alzheimer´s, Familial Amyloidotic Polyneuropathy (FAP) and atherosclerosis. Amyloid fibrils can also be biologically functional. Bacterial and fungal amyloids are proposed to form a prominent protein fold early in evolution. It is unclear why many different proteins, which often assume stable functional quaternary structure under normal conditions, can convert into a common β-sheet rich amyloid aggregate. An important unanswered question is whether the molecular mechanisms of amyloid formation have been conserved in evolution. We will characterize these mechanisms using two very different proteins involved in amyloid diseases: apolipoprotein A-I (apoA-I), a helical protein that is important in atherosclerosis and familial amyloidosis, and transthyretin (TTR), a beta-sheet protein that forms amyloid in FAP. We will explore in detail the novel molecular mechanism of amyloid formation by human apoA-I , which will help design a strategy to block this process. We will further characterize amyloid formation in evolutionary diverse species using fish TTR as a model protein that, we previously showed, forms amyloid. Fish are the most biodiverse group of vertebrates that can adapt to broad range of external conditions; hence, they are particularly suitable to study the adaptation of protein structure/function. TTR amyloid formation will be characterized in two evolutionary distinct piscine species with different adaptation mechanisms: a modern Actinopterygii (sea bream) and an ancient Agnatha (lamprey). The role of sea bream TTR N-terminus, previously proposed to be important in amyloid formation, will be investigated and compared with human TTR. The results will provide sharper insights into amyloid formation by structurally and evolutionaly diverse proteins, and will help develop new strategies to block amyloid diseases such as apoA-I amyloidosis, atherosclerosis and FAP.
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
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IOF
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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
8005-139 FARO
Portugal
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.