Objective
The study of protein aggregates and how they damage neuronal cells is important in order to understand the initiation and progression of several neurodegenerative diseases - including Alzheimer’s disease (AD), Parkinson’s disease (PD). The aggregation from the native monomeric proteins to beta sheet containing amyloid structures involves the formation of different species - misfolded proteins, small soluble oligomers and finally formation of fibrils. It is believed that small oligomers are the most cytotoxic species which play a major role in neuronal loss and cell death. Although, the exact mechanism and extent of amyloid oligomer’s cytotoxicity is still unknown, one of the most consistent pathologies in neurodegenerative disease is unregulated influx of Ca2+ into the cell. Individual oligomers directly disrupt cell membranes through non-specific binding at picomolar concentrations leading to the formation of ion channels, which allow Ca2+ influx and can lead to cell death. Based on this observation, we will develop a single liposome assay to quantify the oligomer induced toxicity from oligomers present in human cerebrospinal fluid (CSF) from healthy controls and patients with AD and PD. Using a Ca2+ sensitive fluorogenic sensor, we will monitor the oligomer induced Ca2+ influx inside the liposome in real time. We will measure and compare the toxicity of synthetic oligomers of amyloid beta, alpha-synuclein, tau and PrP oligomers as a function of oligomer concentration and liposome membrane composition. We will then quantify the effect of various antibodies commonly used for treatment of AD and PD on the toxicity of synthetic oligomers and those in CSF. This novel ultra-sensitive state-of-the-art single molecule technique will provide new insights into the mechanism of oligomer induced toxicity, allowing us to identify the most toxic oligomers and the most suitable antibodies to prevent oligomer induced damage as well as having potential for early disease diagnosis.
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.
- engineering and technology materials engineering amorphous solids amorphous semiconductors
- 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 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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2015
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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.
CB2 1TN CAMBRIDGE
United Kingdom
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.