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Advancing Early Alzheimer’s Disease Detection Through Pan-Phosphorylation Binders and Single-Molecule Nanopore Technology

Project description

Nanopore technology for early detection of Alzheimer’s disease

Early diagnosis of Alzheimer’s disease (AD) remains a major clinical challenge, as the molecular changes underlying the condition begin decades before symptoms appear. Detecting these changes at the single-molecule level could transform early diagnosis and disease monitoring. Nanopore technology allows the identification of individual molecules with exceptional sensitivity, offering the capacity for distinguishing molecular signatures. With the support of the Marie Skłodowska-Curie Actions programme, the SIP-PORE project will develop a nanopore platform capable of detecting specific chemical modifications on AD-related proteins. Technological advances in molecular engineering offer the potential to control protein movement and improve signal clarity. By profiling phosphorylated forms of the key AD biomarkers Tau and APP, the platform will lay the foundation for early, single-molecule AD diagnostics.

Objective

Nanopore single-molecule technology, with its high sensitivity and long-read capability, offers powerful opportunities for protein sequencing and early disease detection. To realize this potential, four steps are essential: protein capture, amino acid and post-translational modification discrimination, controlled translocation, and accurate signal interpretation. Controlled translocation is especially critical for producing clear, distinguishable signals, while robust analysis requires a spectral reference library. This project addresses uncontrolled protein movement by introducing binders that specifically recognize phosphorylation, acting as a “molecular brake” to establish a pan-phosphorylation-binder-assisted nanopore platform. Using this approach, we will map phosphorylated Tau and APP—key Alzheimer’s disease biomarkers—laying the foundation for early diagnostic applications. The platform will also expand nanopore capabilities for detecting diverse post-translational modifications and multiple phosphorylated proteins. Our objectives are: (1) to generate a pan-phosphorylation binder pool using protein engineering and a modified PANCS-binder screening system; (2) to build a spectral reference library for phosphorylation types based on dwell-time profiles; and (3) to create single-molecule nanopore profiles for early Alzheimer’s detection.

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
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.

€ 260 347,92
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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