Cell signaling in microgravity: understanding how drugs work for astronauts

About the Project

You will be working with a homebuilt clinostat, a prototype device that can simulate microgravity while supplying mammalian cells held under physiological conditions with nutrients or pharmacological stimuli. A clinostat is a device that simulates a microgravity environment. It can be used on living mammalian cells, bacteria or plant systems to monitor the effect of microgravity on biological systems, albeit its use is also documented in colloids, liquid crystals or granular materials[1,2].

The clinostat works by rotating a sample along a single axis (hereby defined as y) therefore changing periodically the direction of the gravity vector in both of x and z, leading to a an average vectorial sum of zero over time along each of these two axes. Simply put, over time, gravity acts in all directions and sums to zero. The sample is still experiencing, instantaneously, a force; hence this is not equivalent to real microgravity (as achievable, for instance, on the International Space Station science platforms) but is a good approximation of microgravity. Nonetheless, for processes happening on timescales of minutes to hours, simulated microgravity has been shown to mimic several of the effects of real microgravity[3].

The concerted and finely regulated spatial-temporal interplay of several proteins at the cellular membrane, prominently cell membrane receptors, mediates how human cells respond to extracellular stimuli, generating a cascade of 2nd messengers known as

'downstream signaling'. In a project last year, supported by the European Space Agengy and the UK Space Agency, we demonstrated how altered gravity affects downstream signaling mediated by prototypical G protein-coupled receptors (GPCRs), a family of over 800 membrane proteins and prominent drug targets. We could show that the production of the 2nd messenger cAMP upon adrenergic stimulation is enhanced in hypergravity, and decreased in simulated microgravity, confirming earlier reports that had shown that cAMP homeostasis is affected in cellular organisms and single cells exposed to periods of altered gravity. Our hypothesis is that sub-diffraction limit disturbances in the membrane nanotopography of the signalling receptors are responsible.

In this interdisciplinary project, combining hardware development, experiments at European Space Agency ground based facilities, advanced microscopy, cell biology and data analysis, we want to quantitatively extract the relationship between altered gravity and nanoscale membrane receptors arrangement.

Our results have the potential for developing a research area that received only limited earlier attention in microgravity research, namely membrane nanotopography of signaling proteins, which connects to the role altered gravity has in

modulating pharmacology, which has broad impact towards manned flight and space exploration at large.

If you are interested, please approach or send an email to Dr. Paolo Annibale (pa53@st-andrews.ac.uk).

(1) Oluwafemi, Funmilola A., and Adhithiyan Neduncheran. "Analog and simulated microgravity platforms for life sciences research: Their individual capacities, benefits and limitations." Advances in Space Research 69.7 (2022): 2921-2929.

(2) Brungs, Sonja, et al. "Facilities for simulation of microgravity in the ESA ground-based facility programme." Microgravity science and technology 28.3 (2016): 191-203.

(3) Bathe-Peters, M., Sohail, I., Sirbu, A., Schneider, K., Patriarchi, T., Anilkumar, A., ... & Annibale, P. (2025). "Effects of altered gravity on adrenergic-mediated cAMP signalling in intact cells." bioRxiv, 2025-03.