Novel 19F NMR based methods for structural biology of pathological tau protein, an appealing Alzheimer ́s disease therapeutic target

Alzheimer’s disease and other tauopathies pose a formidable clinical challenge as well as several unmet medical needs to find efficient tools and therapies for their prevention, diagnosis and treatment. All tauopathies are associated with aggregation of pathological forms of the tau protein leading to neurofibrillary tangles in the brain, which makes it a promising target for therapy. However, there is still lack of understanding of the factors and conformational changes during tau oligomerization and assembly that result in specific pathologies. The proposed project aims to unravel the structural and dynamic details of the tau assembly pathway towards the pathological forms by establishing innovative approaches based on solution and solid-state nuclear magnetic resonance (NMR). We will build on cutting-edge methodologies and novel approaches for synthesis and incorporation of 19F labelled amino acids and high-sensitivity NMR experiments to obtain structural and functional characterization of the tau protein and its variants in monomeric, oligomeric and filamentous states relevant for disease. The project will heavily benefit from collaboration with partners of the H2020-MSCA-RISE InterTAU project. The project results will form the basis of innovation in the treatment of Alzheimer’s disease and other tauopathies.
Planned total implementation time of the project: 36 months.
Planned referable costs of the project are € 151 470.

Project implementation updates

2020

2nd of January – start of the project.
16th of September – presentation “Solution and solid-state NMR for studying protein aggregation mechanisms” at Axon Neuroscience in Bratislava, Slovakia.

2021

13th of April – TV broadcast featuring interview with PhD student Kristīne Kitoka “Studying proteins to treat Alzheimer’s disease”.
30th of April – participation in European Researcher Night at Latvian Institute of Organic Synthesis with an educational video about NMR spectroscopy and its applications . More info here.