Objective
Transmissible spongiform encephalopathies (TSE) are caused by the ordered aggregation of PrPC into prions consisting of PrPSc. Similar pathogenetic principles operate in Alzheimer’s and Parkin-son’s disease, and a growing list of further diseases whose prevalence is steadily rising. Familial TSE are invariably associated with PrPC mutations, and the dearth of genetic modifiers has hampered our understanding of prion diseases. Therefore, the first objective of my proposal utilizes a cell-based high-throughput quantitative prion replication assay (developed during my previous ERC instalment) for genome-wide unbiased screens employing new genetics tools (CRISPR, siRNA li-braries, next-gen sequencing) to identify modifiers of prion uptake, replication, and secretion. The second objective aims at clarifying the basis of prion neurotoxicity and will be developed along two alleys: (a) we will uncover the molecular basis of spongiosis (the neuronal vacuolation characteristic of prion diseases), which we suspect to be a main driver of pathology, and (b) we will perform CRISPR-based synthetic lethality screens to identify genes that become essential to prion-infected cell lines (which do not experience prion toxicity) and may not be expressed by neurons. The third objective is to understand the function of PrPC in cellular physiology, and focuses on our evidence that (a) PrPC interacts with an orphan G-protein coupled receptor to maintain peripheral myelin integrity and (b) that PrPC may trigger cell death in response to ER stressors. While certain pathways of degeneration will undoubtedly be specific to prion infections, I expect that some targets will prove common to a variety of protein aggregation diseases including Alzheimer’s and Parkinson’s disease, and may perhaps translate into novel diagnostics and therapeutics. Hence the proposed project may not only open new perspectives in prion biology but also yield insights applicable to much more common diseases.
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
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology
- medical and health sciences basic medicine neurology parkinson
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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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
ERC-ADG - Advanced Grant
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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.
(opens in new window) ERC-2014-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
8006 Zurich
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.