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Content archived on 2024-06-18

Intracellular protein aggregation: fitness and evolution

Objective

Protein misfolding and aggregation are associated with an increasing number of human disorders, such as Alzheimer’s disease and Parkinson’s disease. Additionally, the formation of insoluble deposits during recombinant protein production impedes the commercialization of several peptide drugs. Recent computational studies highlight the existence of a selective pressure to escape from protein aggregation; exerted both on protein sequence and gene expression levels. However, direct experimental evidence demonstrating how natural selection shapes protein sequence and concentration in living cells is still missing. The objective of the here presented project is to exploit a simple cellular model to test how protein aggregation is selected in a biological context. For this, we would study the cell fitness of different yeast cell strains expressing proteins with different aggregation propensity and in growth competition. We have generated a system where each strain is marked with a fluorescent reporter that informs about protein expression, localisation and formation of intracellular deposits. Simultaneously, a specific DNA tag informs about the proportion of each strain in the culture at each time point. By this we will evaluate how protein aggregation influences cell fitness, thus deriving evolutionary principles underlying intracellular regulation of protein deposition.

Fields of science (EuroSciVoc)

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2011-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.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

MEDICAL RESEARCH COUNCIL
EU contribution
€ 200 371,80
Address
20 Park Crescent
W1B 1AL LONDON
United Kingdom

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Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
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Total cost

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.

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