Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Functional contributions of ion fluxes to cellular circadian organisation

Funder Wellcome Charity-funded
Recipient organisation University of Edinburgh
Funding £1.4M
Period Jan 2023 — Jan 2029

In plain English

AI plain-English summary

Every living cell keeps time, and that timekeeping depends on the rhythmic rise and fall of magnesium and potassium ions inside the cell. The researchers have already shown that these ions oscillate in concentration over the daily cycle. Now they want to understand how those ion fluxes control the cell’s broader rhythms—its gene activity, protein production, and metabolism. This matters because the molecular clock is fundamental to health. Disrupted circadian rhythms are linked to metabolic disease, cancer, and ageing. Yet most clock research has focused on genes and proteins, not on the ions that may orchestrate them. This project fills that gap by asking how simple charged atoms coordinate complex cellular schedules. If successful, the work will produce a systems-level map of how ion rhythms shape cellular behaviour. This is fundamental science—there is no immediate medical or industrial application. But understanding how a cell uses magnesium and potassium as timekeepers could eventually inform treatments for conditions where the clock goes wrong, such as jet lag, shift-work disorders, or metabolic syndrome. Past discoveries about ion channels, for example, led directly to drugs for heart arrhythmia and epilepsy.

View original technical description
Our recent work revealed that circadian rhythms exist in the intracellular concentrations of key ions fundamental to cellular life: magnesium and potassium. We now propose a creative research programme around the central hypothesis that fluxes of ions provide key regulatory functions in the circadian organisation of the cellular landscape. Objective 1 is to delineate ion concentration rhythms at the sub-cellular level and use multi-omics techniques to reveal how these integrate into the rhythmic transcriptome, proteome, and metabolome over the diurnal and circadian cycle. Objective 2 will reveal the full cellular magnesium transport machinery of a eukaryotic cell and use gene editing and live cell imaging to visualise the dynamics subcellular magnesium fluxes, as well as long-term adaptation experiments to identify those cellular functions that are sensitive to magnesium rhythms. Objective 3 will investigate the functional effects of potassium concentration rhythms in progression of the cell cycle, in gatekeeping glycolysis and primary metabolism, and in facilitating regulated cellular proteostasis throughout the cell and circadian cycles. Overall, the program will deliver systems level understanding of spatiotemporal ion fluxes and their key roles in the rhythmic orchestration of cellular properties that are fundamental to the health of a eukaryotic cell.

View the original record at the funder ↗

Researchers

Gerben van Ooijen (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Functional & biochemical characterisation of circadian timekeeping mechanisms in mammalian cells
Quantification of protein dynamics driving the circadian clock
Investigation of the role of calcium in circadian rhythms
Modelling ion homeostasis in the yeast Saccharomyces cerevisiae (TRANSLUCENT-2)
Regulation of cellular metabolism and intercellular communication by sodium signaling

Original classification

Discovery Award

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