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Robin Vermathen

Robin Vermathen


Eindhoven University of Technology


Medical Sciences and Technology


Yann Fichou

Faculty Sponsor(s): 

Song-I Han

Faculty Sponsor's Department: 

Chemical Engineering
Chemistry and Biochemistry

Project Title: 

Insights in the Interprotein Signal of DEER Measurements on Aggregates of Tau

Project Description: 

Double Electron-Electron Resonance (DEER) is a technique that uses electron paramagnetic resonance to measure the distance between two unpaired electrons. When these electrons are site-specifically introduced in a protein in the form of spin labels, intraprotein distance measurements can provide information on the three-dimensional structure of the protein. Specifically, this technique can be used to study the behavior of the aggregates of the intrinsically disordered protein Tau, which are associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s, among others. Distinguishing between the signal caused by intra- and interprotein interactions is key in gaining valuable information from DEER measurements. In this research, the behavior of the interprotein signal was studied using singly labeled Tau protein. This signal is described as V_INTER (t)=exp⁡(α∙t^(D/3) ), with the dimensionality (D) being related to the shape of the signal and α being related to the spin-density in the sample. Measurements were performed under various circumstances in order to gain insights into how this signal behaves. For aggregates of Tau, D was found to be approximately 1.5, as appose to the previously assumed 3. Implementing this in signal correction for intraprotein measurements increased the accuracy of the distance measurements. Additionally, steps were made to acquire structural information from the background measurements. More data is needed to understand the changes in D and α under different circumstances, and to quantify the behavior of these variables. In the future, the steps made in this research could contribute to a better understanding of Tau aggregation and the use of DEER to acquire information.