Engineering circadian biology into induced pluripotent stem cell organ-on-a-chip models

Why did we fund this project?

This award aims to introduce circadian rhythmicity to induced pluripotent stem cell (iPSC)-derived organ-on-a-chip models to replace the use of mice in drug evaluation studies.

Dysfunction in the internal body “clock”, or circadian cycle, is a causal factor in ageing and many diseases. Over 80% of proteins that are druggable targets are affected by the circadian clock and are likely to benefit from timed administration. Drug efficacy studies are usually performed in mice, however mice are nocturnal and poorly predictive of human circadian biology and this contributes to late-stage failure in drug discovery programmes. Current organ-on-a-chip models used to evaluate drug efficacy do not incorporate circadian rhythms, limiting the replacement, therapeutic and commercial potential of the technology. Professor David Lee and colleagues will luminescently tag key genes that control circadian rhythms in human iPSCs before differentiating into endothelial and smooth muscle cells and growing them in an organ-on-a-chip device. David will demonstrate the utility of the model in drug evaluation by inducing circadian rhythms in the cells and monitoring emitted luminescence. 

This award was made as part of the BBSRC/NC3Rs joint call for the development of next generation non-animal technologies (NATs).