Circadian (about daily) rhythms are driven by endogenous clocks within every cell that time most aspects of our physiology to a 24h beat. Disruption of daily timekeeping, in aging or shift-work, is strongly linked with increased risk of diseases such as diabetes, Alzheimer’s and various cancers. To understand why, we need to understand the fundamental molecular mechanisms that allow mammalian cells to maintain their daily rhythm, in vitro and in vivo.
The last 20 years has seen the identification of several proteins and cellular systems that are necessary for circadian timing, but how they work together to generate self-sustained and robust rhythms in cellular function is poorly understood. You will work as part of a dynamic and multi-disciplinary team to understand how allow mammalian cells and tissues keep daily time.
The successful applicant should have a degree in biochemistry, cell biology or a related area. You should be enthusiastic and creative with good communication, organisational and numeracy skills. Scientific computing skills and prior lab experience would be useful but not essential. Techniques you will learn include real-time bioluminescence imaging, quantitative mass spectrometry, transgenic complementation, genome editing, mouse behavioural assays, and the opto-/chemigenetic manipulation of protein activity in living cells. You will use these tools to identify the critical steps that license progression through the circadian cycle. Ultimately, you will make a biological clock that can run faster or slower, at the flick of a post-translational switch.
If you share our interest in biological rhythms and would like to work with us, please get in touch to find out more.
References
Stangherlin et al., (2021)
Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology
Nat Comms, 12(1):6035.
Putker et al., (2021)
CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping
EMBO J, 40(7):e106745.
Crosby et al., (2019)
Insulin/IGF-1 Drives PERIOD Synthesis to Entrain Circadian Rhythms with Feeding Time
Cell, 177(4):896-909.e20.