Investigating the effect of electric fields on cellular metabolism.

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Metabolic overflow is the seemingly uneconomical process where metabolism shifts from the exclusive use of respiration to fermentation or respire-fermentation even in the presence of oxygen. Metabolic overflow is ubiquitous in nature, found in both microbial, mammalian and plant cells, and is shown to underpin higher-level processes such as cell growth, dormancy, and differentiation, and multi-cell communication and interactions. Despite this fundamental role, the molecular mechanisms leading to metabolic overflow and its relation to cellular biophysical parameters, such as membrane potential and cellular redox state remains unknown. This project will study overflow metabolism using a combination of metabolic, electrophysiological, and fluorescent microscopy techniques, with the aim to better understand the relation between metabolic overflow, cellular redox state, and membrane potential. Investigations will use single-cell electrophysiological measurements such as pH, membrane potential and redox state in yeast and mammalian cells along with other cellular measurements such as ATP, NADH and metabolite measurements. This information will not only be vital to understand the molecular mechanisms of metabolic overflow, but will possibly pave the way to its manipulation through external electrical field stimulation.