Essentially every cell in a complex organism carries an autonomous ~24-hour oscillator: a transcription-translation feedback loop that drives rhythmic expression of 10–40% of the transcriptome in a tissue-specific pattern. Our new 8-module course, suitable for undergraduates with molecular biology background and for graduate students entering chronobiology, neuroscience, oncology or sleep medicine, covers this oscillator from the founding behavioural experiments through the 2017 Nobel-winning molecular architecture to the clinical discipline of chronotherapy.
Eight Modules
- M0 — Biological Clocks: Pittendrigh and Aschoff, free-running periods, temperature compensation, the 2017 Nobel Prize (Hall, Rosbash, Young), clocks across kingdoms from cyanobacteria to mammals.
- M1 — Molecular Clockwork: CLOCK/BMAL1 activator, PER/CRY repressor, the TTFL’s ~24 h oscillation, Goldbeter-style ODE simulation, CK1δ/ε phosphorylation setting period, FASPS and DSPD mutations.
- M2 — SCN & Peripheral Clocks: ~20 000 SCN neurones, VIP/AVP coupling, autonomous peripheral oscillators in liver/pancreas/muscle/heart, hierarchical coordination via cortisol, temperature, feeding.
- M3 — Light Entrainment: ipRGCs and melanopsin (OPN4), retinohypothalamic tract, Khalsa human phase-response curve, non-image-forming vision, non-photic Zeitgebers.
- M4 — Circadian Cell Cycle: Wee1 and G2/M gating, clock control of cyclin D/E, DNA-damage response rhythm, clock-gene tumour suppression, Fu & Lee 2002 Per2-KO cancer link.
- M5 — Chronometabolism: feeding as peripheral Zeitgeber, NAD+/SIRT1 feedback, time-restricted eating (Panda lab), REV-ERB drug targets, shift work and metabolic syndrome.
- M6 — Sleep, Mood & Mental Health: Borbély two-process model, melatonin pharmacology (tasimelteon, agomelatine), DSPS/FASPS, depression and bipolar disorder, social jet lag in adolescents.
- M7 — Disease & Chronotherapy: time-of-day disease clustering (MI, stroke, asthma), shift work as WHO IARC Group 2A carcinogen, jet-lag management, Lévi colorectal chemotherapy chronomodulation, Hermida blood-pressure trials, drug pharmacokinetic circadian variation.
Featured Lecture
The course landing page embeds Clocks and Human Health, the definitive survey of how biological clocks regulate every aspect of human physiology. Watch it first as an overview, then return through Modules 6 and 7 as the clinical implications deepen.
Python Simulations
Each module includes executable simulations: Goldbeter TTFL oscillation with phase-plane visualisation of the limit cycle, human phase-response curve based on Khalsa et al. (2003), and several others. Run them in the browser and adjust parameters.