TIPPING POINTS IN LIPID-PROTEIN CO-ASSEMBLY

α-synuclein is an intrinsically disordered protein implicated in synaptic vesicle trafficking.

Accumulation of α-synuclein in the form of amyloid deposits coincides with the loss of dopaminergic neurons in Parkinson´s disease. These deposits have been shown to also contain lipids.

It is thus clear that α-synuclein  may switch from vesicle-bound state (lipid-rich co-assembly) to lipid-containing fibrils (protein-rich co-assembly).

This project addresses the question: What are the molecular driving forces that make the protein-lipid co-assembly to go one direction or the other?

The research aims to reach a understanding the underlying physico-chemical mechanisms, and it can add to the understanding of both healthy and disease functions of aSyn.

Specific aims of the project include:1) Unravelling the origin of the cooperative aSyn binding to lipid membranes2) Fundamental understanding of the threshold conditions for membrane-induced aSyn amyloid formation3) Investigating the possibility of vesicle-induced liquid-liquid phase separation in aSyn-vesicle systems.The proposed research is problem-oriented and employs several techniques, including methods that provide information at the single-vesicle level, fluorescence spectroscopy, fluorescence and light microscopy, cryo-TEM, NMR and scattering methods.

The experiments will be combined with thermodynamic analysis.The project is centered around 1 PhD project (4-years) situated within the excellence center COMMONS.