A new phase in understanding Alzheimer’s disease: Identification and characterization of the relationship between Tau liquid-liquid phase separation and cellular consequences

Liquid-liquid phase separation (LLPS) is an interesting process both from a chemical and biological point of view. LLPS has been implicated as important for Tau protein associated with Alzheimer’s disease (AD).

In this project the process of Tau droplet formation by LLPS will be extensively studied with two aims:To investigate how and why physiologically relevant molecules modulate Tau LLPS by elucidating structural details and functionality.To study the consequences of Tau LLPS for cells and other proteins, such as toxicity, and perturbation of cellular components.This 3-year project is to be carried out by the applicant with 2/3 of the project allocated at the Paul Scherrer Institute in Switzerland and 1/3 at Karolinska Institutet.

Beyond research facilities at the applicants’ disposal, valuable expertise and knowledge in the groups are provided.

Several techniques will be implemented, such as crystallization robotics, fluorescence spectroscopy, nuclear magnetic resonance, SAXS/SANS, cryo electron tomography, single-channel electrical recording, and cell viability assays.

The goal of this project is to connect the phenomenon of LLPS to Tau protein in AD and at the same time study the corresponding cellular effects with a new approach – both from a structural point of view and to functionality and toxicity.

The outcome of this project will bridge current knowledge to entirely new findings relevant for a molecular understanding of AD.