Alessandra Stangherlin

FM | Institute for Mitochondrial Diseases and Ageing (CECAD)

Research Areas


Circadian rhythms, cellular homeostasis, and ageing

Our overarching goal is to unravel the mechanisms behind the circadian regulation of cell function and understand how the ageing process impacts these fundamental processes.

Research Focus

Our research aims to unravel the complex mechanisms governing circadian rhythms (approximately 24 hours) in cellular function and physiology, which align organisms to the environmental light/dark cycle. Misalignment with external time, for example during repetitive jet lag and night shift work, correlates with disease susceptibility and reduced lifespan. The root causes are poorly understood.

A recent breakthrough in our research revealed that intracellular ion abundance follows a circadian rhythm. This rhythm plays a vital role in preserving osmotic homeostasis and cell volume while also contributing to the time-of-day variations in cardiomyocyte action potential firing, thus influencing daily fluctuations in heart rate. Our ongoing investigations are focused on identifying the underlying mechanisms and examining how these processes are affected during the ageing process.

Implementing new strategies to preserve body clocks may hold the key to delaying ageing and age-associated diseases.

Our Goals

Our research is dedicated to unravelling the mechanisms governing circadian ion rhythms and their impact on cellular functions.

  • We employ a diverse array of cutting-edge techniques, ranging from live-cell bioluminescence assays to observe the cellular circadian clock to microwave plasma atomic emission spectroscopy for in-depth analysis of the elemental composition of cells and tissues.
  • We are actively working to increase the spatial resolution for monitoring essential elements such as Na, K, Mg, and Ca at the subcellular level using fluorescent dyes and genetically encoded sensors.

Our goal is not only to decipher generic mechanisms that sustain circadian ion rhythms and cell functions but also to understand how cellular clocks are affected by ageing. Our long-term objective is to design targeted interventions that restore cellular circadian rhythms, thereby delaying the onset of age-related diseases.

Key Publications

  1. Stangherlin, A. (2023). Ion dynamics and the regulation of circadian cellular physiology. Am J Physiol Cell Physiol.
  2. Wong, D.C.S., Seinkmane, E., Zeng, A., Stangherlin, A., Rzechorzek, N.M., Beale, A.D., Day, J., Reed, M., Peak-Chew, S.Y., Styles, C.T., et al. (2022). CRYPTOCHROMES promote daily protein homeostasis. EMBO J
  3. Stangherlin, A., Watson, J.L., Wong, D.C.S., Barbiero, S., Zeng, A., Seinkmane, E., Chew, S.P., Beale, A.D., Hayter, E.A., Guna, A., et al. (2021). Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology. Nat Commun.
  4. Stangherlin, A., Day, J., and O'Neill, J. (2021). Inductively Coupled Plasma Mass Spectrometry for Elemental Analysis in Circadian Biology. Methods Mol Biol.
  5. Stangherlin, A., Seinkmane, E., and O'Neill, J.S. (2021). Understanding circadian regulation of mammalian cell function, protein homeostasis, and metabolism. Curr Opin Syst Biol.


Research Areas