Many commonly used drugs would benefit from considering daily biological timing but mechanistic understanding of circadian medicine is limited. Traditional in vitro models do not recapitulate diurnal rhythms in human physiology because they lack the daily systemic cues encountered in vivo, whereas lab mice are problematic due to their nocturnal physiology.
Working within an inclusive multi-disciplinary team, this ambitious project will fill a critical innovation gap by refining our cutting-edge multiplexed microfludic systems to hormonally synchronise daily rhythms in cultured human cells and iPSC-derived tissues. This will allow diurnal physiology to be modelled in a dish, validating initial findings against published human data and observations from the diurnal striped mouse (Rhabdomys pumillio).
By monitoring circadian rhythms at the level of the population and individual cell, you will address the molecular mechanism(s) by which, in vivo, cells integrate a diversity of fluctuating extracellular signals so that daily clocks in different tissues remain synchronised with each other and day/night cycles, and how they re-entrain after shift work or jet lag.
In parallel, you will establish the utility of this approach for pre-clinical research by assessing whether daily variation in drug toxicity and/or efficacy, observed in vivo, can be recapitulated in vitro.
Techniques will include cell culture, long-term monitoring of genetically-encoded bioluminescent and fluorescent reporters, live-cell microscopy, quantitative mass spectrometry, machine learning, transgenic complementation, genome editing and opto-/chemigenetics.
The successful applicant will have a degree in biochemistry, cell biology or a related area. You should be enthusiastic and creative with good communication, organisational and numeracy skills. Previous experience with tissue culture and programming would be desirable but not essential.
If you share our interest in biological timing and would like to work with us, please get in touch to find out more.