Project description
Identifying modulators of tau amyloid formation
Protein dysfunction is at the root of many pathologies. The Tau protein, mostly present in neurons, aggregate into amyloid fibrils, a hallmark of several diseases including Alzheimer’s. However, the mechanisms of tau amyloid formation remains unclear. The EU-funded cofacTau project will investigate tau aggregation in the presence of various biologically relevant co-factors. With advanced biochemical and biophysical techniques, the team will attempt to identify which factors modulate tau aggregation pathways and structural differentiation. Success will afford new insights into disease pathways and provide basis for new drug development strategies.
Objective
"Tau is an intrinsically disordered protein that regulates microtubule activity in neurons. Aggregation of tau into amyloid fibrils is diagnostic of several diseases, termed tauopathies, that include Alzheimer's disease. Distinct amyloid aggregate structures, so-called ""strains"", are involved in different tauopathies. These assemblies can spread and recapitulate pathological phenotypes when injected in cells and animals. This is the hallmark that tau aggregates follow a prion behaviour. To date, the factors guiding the formation or propagation of specific strains are unknown. Showcasing this crucial gap in knowledge is the fact that none of the brain-extracted tau amyloid structures has been reproduced in vitro. This project intends to establish a paradigm shift for the very definition of tau strain. I propose the novel hypothesis that the co-aggregation of tau with other biomolecules such as lipids or polyanions, so-called cofactors, is a defining property of tau prion strains. To demonstrate this hypothesis, I will test that the tau-cofactor interactions (i) dictate the structure of tau aggregates, (ii) enable structure replication through seeding and (iii) dictate the neuropathology developed in cells and mice after inoculation of tau seeds. My approach is to study the pathological properties and the conformational evolution of tau aggregates in the presence of biologically-relevant cofactors possessing different physico-chemical properties. By mapping the interactions between tau and cofactors, my goal is also to establish the canonical rules governing tau structural differentiation. This proposal combines multiple methods including EPR and NMR spectroscopy, AFM-based nanospectroscopy, biochemistry, cell biology and animal histology. The proposed paradigm shift would have a very high impact in the field of tauopathies, for example by enabling accurate structure-based drug discovery, revealing new drug targets and pinpointing key deleterious metabolic pathways.
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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.
This project's classification has been validated by the project's team.
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.
This project's classification has been validated by the project's team.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences biophysics
- natural sciences biological sciences histology
- natural sciences biological sciences molecular biology structural biology
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.
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HORIZON.1.1 - 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.
HORIZON-ERC - HORIZON ERC Grants
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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-2021-STG
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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.
75794 PARIS
France
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.