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Jule van Basten

Jule van Basten


Eindhoven University of Technology


Chemical Engineering and Chemistry


Yann Fichou

Faculty Sponsor(s): 

Songi Han

Faculty Sponsor's Department: 

Chemical Engineering
Chemistry and Biochemistry

Project Title: 

Identifying Conformational Changes of Tau Protein Activated Upon Aggregation Using EPR Spectroscopy

Project Description: 

Neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Huntington’s and Parkinson’s disease represent an important socio-economic burden for modern society and their prevalence is expected to grow in the coming decades. Several proteins are associated with NDs, including Tau. Tau is abundant in neurons where it stabilizes the neuronal microtubule by binding to the microtubule with its four repeat domains. In pathological conditions, single Tau monomers can form β-sheet structured species that can aggregate into so-called amyloid fibers, which is one of the hallmarks for AD and other tau-associated diseases. The aggregation pathway of Tau still is unclear. Here, we research a tau fragment, referred to as ∆ Tau187, which is prone to form amyloid fibers, to analyze the aggregation pathway of Tau. We do this by measuring conformational changes adjacent and inside the four repeat domains of ∆ Tau187 with a specific electron paramagnetic resonance (EPR) spectroscopy method called Double Electron-Electron Resonance (DEER) and continuous wave EPR. DEER relies on site directed paramagnetic electron spin labeling of ∆ Tau187 and can measure intra-molecular distances between these paramagnetic probes. Our results suggest early conformational changes in the microtubule repeat domains of ∆ Tau187 before the monomer forms β-sheet structured species. Furthermore we show several conformational changes in specific regions of ∆ Tau187 between monomeric and amyloid fibers of ∆ Tau187, which is a clear step towards understanding the aggregation pathway of Tau.