A new platform to understand and control protein liquid-liquid phase separation

Proteins can undergo liquid-liquid phase separation (LLPS) and form liquid droplets. This self-assembly mechanism plays a central role in biology and disease (e.g. Alzheimer's and Parkinson's disease). Nevertheless, it is still largely uncharacterised due to the lack of analytical tools to monitor it in biologically relevant complex systems, such as cells. Environmentally responsive probes offer unparalleled opportunities to probe biomolecular self-assembly events in cells and provide a read-out for their location, timing, and downstream consequences.

In this project, we will deliver a platform to quantitatively monitor LLPS in live cells, for the first time. We will investigate a-synuclein, a crucial protein of the nervous system, whose LLPS has been hypothesised to be important for the protein's normal function and for inducing amyloid aggregation linked to Parkinson's disease. This multidisciplinary project will involve a combination of biophysical protein characterisation, optical probe development and live cell microscopy.