Dynamics of metabolically-active biomolecular condensates

Membraneless organelles are functional subcellular structures that have been receiving increasing interest and attention in the biosciences community. Unlike the better-known membrane-bound organelles, these dense liquid-like biomolecular condensates freely exchange molecules with their surrounding environment. Mechanisms of phase separation, an equilibrium process, are thought to strongly influence the formation of these condensates. However, life exists far from equilibrium and therefore new insights are required to understand the properties of biomolecular condensates out of equilibrium. Processes that drive living cells from equilibrium include the metabolic reactions of enzymes and ion gradients, such as the proton gradients utilised in bioenergetics.

This project will investigate synthetic biomolecular condensates encapsulating enzyme reactions that exhibit pH-dependent autocatalytic feedback mechanisms. This will allow us to explore the properties and behaviours of the condensates far from equilibrium. Systems will be designed with mutual, coupled dependencies between the condensation and enzyme reaction processes, giving rise to complex nonlinear dynamical properties. This may lead to autonomous oscillations, analagous to temporal biochemical cycles in living organisms. A combination of biophysics, biochemistry and chemical biology techniques will be applied to manipulate and study these biomimetic reaction-condensation processes, providing broad interdisciplinary training to the student. In particular the student will gain expertise in biomolecular engineering, time-resolved confocal fluorescence microscopy and fluorescence spectroscopy methods.

New insights will be gained into the mechanisms that govern the behaviour of natural biomolecular condensates as well as enabling the design of artificial condensates for engineering biology applications, such as the development of smart bioinspired materials for advanced drug delivery systems.