Molecular Horizons Seminar - Dr Yi Shen

There is a rising recognition that a wide range of biomolecules can undergo a liquid-liquid phase separation, forming condensates in cells. These membraneless organelles are normally rich in molecules, highly dynamic and carrying out important functions in biological systems. Crucially, a further liquid-to-solid transition of the condensates can lead to pathological aggregation and cellular dysfunction, causing diseases, such as neurodegenerative disorders. Despite the importance of liquid-to-solid transition of proteins, the mechanism of the onset and development of it remains unexplored. Here we demonstrate a scattering based optical approach and other soft matter methods to detect and monitor the dynamics of the molecules within condensates. We were able to resolve the internal structure of the condensates through the phase transitions. The results indicate the changes in structure, dynamics and mechanics of the condensates as a function of time and space. This discovery and methodology have provided new identifying strategies to broaden the threshold and prevent progression of pathological assemblies in protein aggregation related diseases.