Objective
Protein aggregation diseases are associated with the intracellular accumulation of specific misfolded protein aggregates, that are directly implicated in cellular dysfunction. A range of human disorders of previously unknown nature now falls into this category. The mechanisms of aggregation-induced cell degeneration are however unclear, resulting in poor therapeutic strategies. In this project we will characterize the network of cellular responses to a set of disease-related aggregation-prone proteins (APPs) and determine how to efficiently modulate proteotoxicity. In a discovery phase, we will use proteome-wide screens to identify functional modules that sequentially respond to APP aggregation. A novel method to probe conformational changes of proteins in their biological matrix will be applied to quantify concomitant changes in APP conformation during the toxicity cascade. Our eminently quantitative approach will allow us to characterize the kinetics of intracellular aggregate formation and the resulting cellular responses. A set of biological markers for different functional modules and toxicity stages will be measured using a selected reaction monitoring-fingerprint assay, through a set of genetic and chemical modulators of proteotoxicity. This will unravel how modulators rewire or compensate for the deregulated networks and suggest their most efficient combinations. The multi-level information will be iteratively integrated with prior data and network structure. Emerging hypotheses will be tested using a combination of genetic and biochemical tools and targeted proteomic experiments. This project features novel concepts and methods and will allow us to unravel the molecular events accompanying the onset of proteinopathies and their modulation. It will positively impact biomedical research on protein aggregation diseases, guide identification of suitable therapeutic strategies and advance our understanding of the biology of 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.
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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.
ERC-2013-StG
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.
Host institution
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.