Clocks across taxa: Conserved circadian timekeeping mechanisms

Earth's rotation around its axis causes daily changes to the environment, influencing the metabolism and physiology of organisms since the first life on earth. An endogenous timekeeping mechanism, the circadian clock, evolved to allow anticipation of the daily cycle and drive circadian rhythms such as the sleep-wake cycle in animals or the synthesis and degradation of starch in plants.

The rhythmic expression of 'clock genes' was long thought to cause rhythmic metabolism, until we recently established that clock gene rhythms are dispensable for some metabolic rhythms in organisms as diverse as algae and humans [1-2]. Moreover, we found that metabolic rhythms could contribute to global gene expression rhythms, shifting the paradigm of what constitutes 'the clock' from only gene expression networks to include metabolism [3]. We recently reported in Nature that circadian rhythms in the intracellular concentration of magnesium ions act as a cell-autonomous timekeeping mechanism, determining key clock properties both in a unicellular alga and in human cells [3]. Mechanistically, we found that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression.

The novel metabolic circadian rhythms we identified are conserved across eukaryotic life, spanning over a billion years of evolution. A key aspect of our research is to use that conservation to our advantage in 'comparative chronobiology' studies. For these studies, we use experimental model cells to efficiently test the most stimulating hypotheses and generate new ideas that can subsequently be translated into more complex organisms such as plants, mammals, or fungi. Our model eukaryotic species, Ostreococcus tauri, offers unique advantages over any other cell type. This marine alga is unicellular, contains a haploid genome of only ~8000 genes, and a cellular structure of reduced complexity. It is convenient to grow, experimentally highly tractable, and now a well-established circadian clock model organism.

Using Ostreococcus we will address the fundamental knowledge gap between circadian gene expression cycles on one hand, and the biochemical mechanisms that ultimately facilitate rhythmic cell biology on the other. The successful candidate will join our team and gain a highly diverse training programme in general molecular biology, tissue culture, and biochemistry techniques, as well as specific experimental design for chronobiology, extensive in vivo luciferase imaging, chemical biology, and transgenic approaches in algae.