Project description
Structure determination of protein aggregates in Alzheimer’s disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting mainly the elderly population. It is characterised by the accumulation of amyloid beta and tau protein aggregates in neuronal cells. Despite their confirmed neurotoxicity, these protein oligomers have not been structurally characterised in detail. The scope of the EU-funded Oligomers-MAS-NMR project is to determine the structure and interaction of amyloid beta and tau oligomers using cutting-edge technologies. Project results will provide fundamental knowledge in protein misfolding and aggregation in AD, opening new possibilities for the design of novel treatment strategies.
Objective
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder responsible for about 2 million deaths per year. Despite tremendous progress in basic research within the last years, its efficient treatment and diagnostic tools are still lacking. The previous studies have gathered sufficient evidence of a causative role of the aggregates of two proteins - amyloid beta and tau - in the AD pathogenesis. Both of these proteins can form highly toxic oligomeric species, which are the primary suspects of AD-related neurotoxicity. However, due to experimental difficulties the detailed structural and functional characterization of the oligomeric forms has been a big challenge. In the proposed project we aim to build on cutting-edge technologies and novel approaches to obtain atomic-level structures and investigate interactions of the amyloid beta and tau oligomers. Thus, this multidisciplinary project will apply (I) cell-free protein expression and purification protocols for incorporation of various selectively 13C, 15N and 19F labeled amino-acids; (II) microfluidics in order to generate size-controlled oligomers (III) solid-state NMR (ssNMR) at fast magic-angle spinning (MAS) regime tailored for 1H and 19F detection schemes. The anticipated outcome of this will be a unique combination of approaches to study amyloid aggregates, which can be further used and adapted for studying other protein assemblies. The project results will form the basis of innovation in the treatment of AD as well as other tauopathies.
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Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
LV-1006 Riga
Latvia