Parkinson’s disease affects 10 million people worldwide. It is characterised by the accumulation of protein aggregates in nerve cells. These aggregates are composed of a protein called alpha-synuclein (α-syn). Recent evidence suggests that α-syn can undergo liquid-liquid phase separation (LLPS), forming dense protein phases. The latter may trigger aggregation.

However, due to a lack of techniques capable of examining the early stages of LLPS, the link between α-syn aggregation and LLPS remains unclear. Current strategies focus on temporal scales at which LLPS is already in place (seconds, minutes or hours), which prevents access to the early phases (sub-second range) of condensation.

This pilot project will exploit the potential of combining a cutting-edge time-resolved small-angle X-ray scattering (TR SAXS) technique with computer simulations. The former enables the real-time investigation of LLPS formation with an unprecedented temporal resolution of up to milliseconds. The latter will complement the experimental outcomes with a molecular view of the phenomena. By integrating these methods, we aim to identify the key factors that initiate α-syn LLPS, understand their individual contributions, create comprehensive phase diagrams and ultimately reveal the molecular processes involved in LLPS formation. The outcomes of this project could provide a new screening tool for drugs against Parkinson’s disease.

For more information, contact:

Marco Polimeni
University of Copenhagen
marco.polimeni@sund.ku.dk