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Characterising protein oligomers and their role in neurodegenerative disease in humans

Objective

Small soluble protein aggregates play a key role in the onset and spreading of Alzheimer’s and Parkinson’s diseases. However, which oligomers are present in human disease and which are toxic remains unknown because ultrasensitive methods do not exist to detect and characterise the low concentration of oligomers, which are highly heterogeneous in size and structure. To address this problem we will develop fluorescence based methods to detect and characterise individual oligomers to measure the oligomer size, structure, proteinase K resistance, seeding capability and composition. We will also develop methods to enrich these oligomers so we can use mass spectrometry to determine post translational modifications and recover the oligomers to directly test their cytotoxicity and mechanism of damage. The capability to characterise these oligomers at this unprecedented level of detail will represent a major advance in the field. These methods will then be applied to stem cell models of Alzheimer’s disease and Parkinson’s disease and then clinical samples of CSF from patients. These experiments will determine how the number, composition or structure of the oligomers changes in the disease and if this results in increased cytotoxicity. Clinical samples of CSF from patients with genetic mutations will be used to determine if detectable changes in the oligomers occur early in the disease and samples of brain tissue used to determine the changes in oligomers during the spreading of the disease.

By the end of the project we will have determined which oligomers play major roles in the onset and spreading of Alzheimer’s and Parkinson’s disease in humans, providing targets for therapies, and tested if the detection and characterisation of these oligomers can be used for early diagnosis of the disease.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2014-ADG

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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

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.

€ 2 499 551,00
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 2 499 551,00

Beneficiaries (1)

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