BIO-LLPS

Many membrane-less cellular compartments are formed by liquid-liquid phase separation (LLPS). This process is related to the flexibility and effective charge of macromolecules. The underlying mechanisms and driving forces are still poorly understood. 

BioLLPS is based on a well-defined biological system used by the rabies virus to build viral factories in the infected host cell (called Negri bodies in the case of rabies). This system has unique properties for a biophysicist, as it separates into two liquid phases in a reversible and reproducible manner, and the highly concentrated protein phase remains in a liquid state without aggregation, crystallization, or gelation. This system also has the ability to control the partitioning of other macromolecules between phases. This system offers the possibility to be characterized in terms of structure and colloidal forces, allowing the identification of factors that control LLPS in biological systems. The objective of BioLLPS is to decipher some of the underlying physicochemical principles by which proteins induce LLPS leading to membrane-free organelles in cells. In a bottom-up approach, we will establish a minimalist model system that recapitulates the essential properties of these virus-induced organelles: (1) appearance of a dense liquid phase and (2) partitioning of macromolecules.