Objective
Neurodegenerative diseases (NDs) are an immense burden to patients, their families and society. For decades, they have been defined by two core characteristics. First, different NDs are characterized by the deposition of different toxic proteins in the nervous system, which are critical drivers of disease. Secondly, in different NDs different neuron subtypes are preferentially lost. Uncovering causal mechanisms explaining this selective neuronal vulnerability in NDs has remained difficult due to technical limitations. Here, I will comprehensively model this experimentally to establish the missing link and uncover the molecular mechanisms of how ND-causing toxic proteins cause selective neuronal vulnerability, and how resilient neurons survive. I will use an innovative Drosophila-human cross-species approach that I developed. As a discovery tool, we will perform parallelized single-cell RNA sequencing (scRNA-seq) of hundreds of different mature Drosophila neuron types that are exposed to defined amounts of toxic proteins. Based on the differential responses we will be able to build a holistic atlas of neuron-type-intrinsic vulnerability and resilience mechanisms in response to ND-causing toxic proteins. These will be computationally mapped to human, experimentally assessed in patient brains, and causal mechanisms established in in vivo modifier experiments in flies. We will also assess shared resilience mechanisms, since co-pathology of multiple toxic proteins is common. Therefore, we will employ concomitant protein detection and scRNA-seq to differentiate neuron-type-specific pathways that protect from toxic protein build-up vs. those that protect from the downstream cellular damage. Thereby, we will advance a fundamental scientific question and reverse engineer the brains‘ own resilience mechanisms for a new class of ND treatment targets.
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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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-2026-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.
6020 Innsbruck
Austria
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.