Dr Tim Nott

Dr Tim Nott

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 like this. Cells also contain a variety of organelles and compartments such as nucleoli, Cajal bodies, P-granules and nuage that lack a membrane boundary. These membraneless organelles form by the condensation protein and RNA into liquid-like droplets, and can be readily observed with a light microscope. Membraneless organelles are predominantly associated with DNA and RNA biochemistry, and rapidly assemble and dissolve with changes to the cellular environment or cell cycle.

Our research on model membraneless organelles that the interior is a unique solvent environment, with surprising emergent biochemical properties. For example, model membraneless organelles can selectively absorb and traffic proteins and structured RNAs, and melt nucleic acid duplexes without the input of ATP, essentially acting as passive helicases.

Our major research aims are 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. To tackle these fundamental biological questions, we take an interdisciplinary approach, using tools and techniques from cell biology, structural biology, polymer theory and bioinformatics. Our research is supported by the world-class Micron Advanced Bioimaging Unit and the superb suit of biophysical instruments within the Department of Biochemistry.

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