Undergraduate / Graduate · Chronobiology & Medicine
Circadian Clocks, Cell Cycle & Human Health
How the ~24-hour molecular oscillator in every cell regulates metabolism, the cell cycle, sleep, and disease — from the 2017 Nobel-winning TTFL to chronotherapy in the clinic.
About This Course
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. This oscillator coordinates sleep, feeding, hormone release, body temperature, the cell cycle, immune function, and cognition with the external light-dark cycle. When the oscillator desynchronises from environmental time — jet lag, shift work, circadian disease — the consequences include metabolic syndrome, cancer, cardiovascular events, and mood disorders.
This 8-module course takes you from Pittendrigh’s founding free-run experiments and the 2017 Nobel-winning molecular clockwork, through central/peripheral clock architecture, light entrainment, circadian control of the cell cycle and metabolism, sleep and mental health, and finally to the emerging clinical discipline of chronotherapy. Suitable for undergraduates with one course of molecular biology and for graduate students entering chronobiology, neuroscience, oncology, or sleep medicine.
Featured Lecture — Clocks and Human Health
The definitive survey lecture on how biological clocks regulate every aspect of human physiology and why circadian disruption has become a major 21st-century health concern. Recommended viewing before Module 0 and as a return reference through the clinical modules (M6–M7).
Key Concepts
Free-run period (τ)
Endogenous period in constant darkness (DD); human ~24.2 h
TTFL (core oscillator)
CLOCK/BMAL1 → PER/CRY → inhibit CLOCK/BMAL1 → ~24 h cycle
Phase response curve
ΔΦ(t) vs stimulus time — advances, delays, dead zone
Two-process model
S (homeostatic) + C (circadian) = sleep propensity
Clock-controlled genes
10–40% of tissue transcriptome oscillates
IARC Group 2A
Shift work "probably carcinogenic to humans" (WHO 2019)
Eight Modules
M0
Biological Clocks
Pittendrigh/Aschoff founding experiments, DD and LD free-run periods, chronotypes, the 2017 Nobel Prize (Hall, Rosbash, Young), clocks across kingdoms from cyanobacteria KaiABC to mammalian SCN.
M1
Molecular Clockwork
CLOCK/BMAL1 activator, PER1/2/3 and CRY1/2 repressors, the transcription-translation feedback loop (TTFL), phosphorylation cascades (CK1δ/ε, FBXL3), ~24 h oscillation emergence from protein turnover.
M2
SCN & Peripheral Clocks
Suprachiasmatic nucleus (20,000 neurons), VIP/AVP coupling, peripheral oscillators in liver/kidney/gut/muscle, phase coupling through hormones (cortisol, melatonin) and autonomic outputs.
M3
Light Entrainment
Intrinsically photosensitive retinal ganglion cells (ipRGCs), melanopsin (OPN4), retinohypothalamic tract (RHT), phase response curves, non-image-forming vision, blue-light effects.
M4
Circadian Cell Cycle
Wee1, cyclin D/E regulation by clock components, gated G2/M transition, DNA-damage checkpoints tied to circadian time, implications for cancer chronotherapy.
M5
Chronometabolism & Feeding
Feeding as peripheral Zeitgeber, NAD+/SIRT1, time-restricted eating (Panda, Longo), REV-ERBα, nuclear-receptor circadian crosstalk, shift work and metabolic syndrome.
M6
Sleep, Mood & Mental Health
Two-process model (Borbely), sleep-wake homeostasis, circadian amplitude in depression, bipolar mood cycling, delayed sleep phase syndrome (FASPS/DSPS), bright-light therapy.
M7
Disease & Chronotherapy
Cancer incidence in shift workers (IARC Group 2A), cardiovascular events by time of day, chemotherapy chronomodulation (Levi), drug dosing considerations, jet-lag management.
Cross-Links
Cell Physiology,Neuroscience,Mitochondria,Organelles,Stem Cells,Pharmacology.
Foundational References
- [1] Pittendrigh, C. S. (1960). Circadian rhythms and the circadian organization of living systems. Cold Spring Harb. Symp. Quant. Biol., 25, 159–184.
- [2] Konopka, R. J. & Benzer, S. (1971). Clock mutants of Drosophila melanogaster. PNAS, 68, 2112–2116.
- [3] Takahashi, J. S. (2017). Transcriptional architecture of the mammalian circadian clock. Nat. Rev. Genet., 18, 164–179.
- [4] Bass, J. & Takahashi, J. S. (2010). Circadian integration of metabolism and energetics. Science, 330, 1349–1354.
- [5] Hastings, M. H., Maywood, E. S. & Brancaccio, M. (2018). Generation of circadian rhythms in the suprachiasmatic nucleus. Nat. Rev. Neurosci., 19, 453–469.
- [6] Panda, S. (2016). Circadian physiology of metabolism. Science, 354, 1008–1015.
- [7] Leví, F. & Schibler, U. (2007). Circadian rhythms: mechanisms and therapeutic implications. Annu. Rev. Pharmacol. Toxicol., 47, 593–628.