In the living cell, virtually nothing stays the same over the day/night cycle. Endogenous ~24h rhythms are driven by a biological timekeeping system, the circadian clock, that dynamically regulates nearly all biological processes to match Earth's environmental cycle. Rhythmic metabolism is achieved in part by clock-controlled gene expression, but the biochemical mechanisms that link rhythmic gene expression to rhythmic cellular metabolism are largely unknown. Our recent work led to the central hypothesis that circadian fluxes of ions into and within the cell provide a critical regulatory function in the reciprocal feedback between transcriptional and metabolic rhythms.
This PhD project will test aspects of this central hypothesis in a species of marine algae (Ostreococcus tauri) as a prototypical eukaryotic model cell. We will investigate the mechanisms through which circadian rhythms in magnesium and/or potassium are generated, and identify functional significance in the context of wider cell biology and metabolic rhythms. This might involve delineating sub-cellular ion fluxes over time and contextualising them along the membrane proteome rhythms that explain them, followed up by gene editing of membrane proteins. Subsequently, circadian gene expression will involve longitudinal luminescent imaging of reporter lines. We will also establish rhythmicity in the metabolic network and identify the harmonics with underlying transcript, protein, and ion rhythms before probing the causal relationships between cellular information flow and rhythmic metabolism. Through comparative biology, results from our model cells will likely be tested in all eukaryotic kingdoms. Project details will be shaped to the candidate's interests and strengths, so if you are interested, please contact Dr. van Ooijen directly so that we can have these initial discussions.
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