Compartmentalisation via liquid-liquid phase separation in cells

A central organising principle of eukaryotic cells is the compartmentalisation of biochemical reactions by membrane boundaries into organelles. However, not all processes are organised in this fashion. Organelles, such as nucleoli, Cajal bodies and P-granules are cellular compartments that lack a membrane boundary. Often spherical in appearance and readily observable with a light microscope, membraneless organelles are highly dynamic and can rapidly assemble and dissolve with changes to the cellular environment. They are predominantly associated with DNA and RNA processing, and have been linked with neurodegenerative diseases and viral infection. Membraneless compartments typically display the properties of liquid droplets. They form by the condensation of material in the cell, in a similar way to how water condenses to form rain drops. Their droplet-like nature makes membraneless organelles particularly challenging to work with and study.

By creating model membraneless organelles, I have shown that their interior is a unique solvent environment, geared towards making certain biochemical reactions involving DNA and RNA more efficient.

I propose to use an approach spanning physics and biology to explain how the liquid properties of membraneless organelles provide a general organising principle in cells, and to understand why cells perform certain reactions inside them.