EP Lecture 4 - Living with Clocks

Benefits of circadian timing

anticipation of daily and seasonal changes improves survival

Why students hate 9am lectures

most chronotypes peak later in the day

Chronotype

individual variation in preferred sleep/wake timing

Teenage chronotype

teenagers wake later; stronger effect in males

Chronotype categories

lion, bear, wolf, dolphin

Lion chronotype

early riser; morning productivity

Bear chronotype

mid‑day productivity; majority of population

Wolf chronotype

late chronotype; afternoon productivity

Dolphin chronotype

light sleepers; irregular patterns

Environmental cues

for entrainment: light, temperature, daylength

Entrainment

synchronisation of internal clock to external cues

Solar cycles

24 h day; 365 day year

Lunar cycles

29.5 day lunar; 14.8 day semilunar; 12.4 h tidal

Need for entrainment

dawn and dusk shift daily

Melanopsin photoreceptor

in intrinsically photosensitive retinal ganglion cells

Melanopsin wavelength

absorbs blue light ~480 nm

Blue light effect

increases PER expression and delays sleep

Night shift mode

reduces blue light to avoid phase delay

Phase resetting

light early night delays; light late night advances

Retinohypothalamic tract

eye → SCN pathway for light entrainment

Seasonal rhythms

organisms adjust physiology to daylength

Synchronous breeders

reproduce at same time yearly (e.g. red deer)

Asynchronous breeders

reproduce year‑round (e.g. Indian chital deer)

Long day breeders

quail; reproduce when days lengthen

Short day breeders

sheep; reproduce when days shorten

Seasonal gene regulation

PER and CRY overlap encodes daylength

TSH seasonal role

regulates breeding transitions

Photoperiodism

seasonal biology controlled by daylength

Reduced seasonality breeds

e.g. Polled Dorset sheep; fertile out of season

Accelerated lambing

three lambings in two years

Plants use daylength

flowering triggered by long days in many species

Arabidopsis flowering

GI, FKF1, CO, FT regulate long‑day flowering

GI tracks dusk

GI expression peaks near dusk

FKF1 expression

peaks ~12 hours after dawn

GI‑FKF1 coincidence

internal coincidence signal

Light stabilises GI‑FKF1

external coincidence signal

CONSTANS (CO)

promotes FT expression and flowering

CO protein stabilised by light

CO and FT accumulate only in long days

Night break

interrupting night with light induces flowering in short‑day plants

Circadian gating

clock filters environmental noise; responses vary by time of day

Environmental noise

temperature and light fluctuate unpredictably

Cold response gating

clock restricts cold‑induced gene expression

Alternative splicing

temperature‑dependent RNA structure affects splicing

RVE2

alternatively spliced during chilling

RVE2 mutants

show altered cold‑response transcription

Jetlag

circadian misalignment after rapid travel

Shift work

increases metabolic and cardiovascular disease risk

Chronic circadian misalignment

increases BMI, diabetes, cancer risk

Aging

clock becomes less robust

Social jetlag

weekend sleep patterns misaligned with weekdays

Chronic jetlag effects

altered gene expression and metabolism

Jetlag and liver

chronic misalignment increases liver fat

Combating jetlag

faster entrainment, light control, molecular manipulation

Natural light exposure

promotes entrainment

Screen light at night

delays circadian phase

BMAL1/CLK complex

transcription factor binding E‑box sequences

E‑box sequences

CACGTG and CACGTT

CLK function

histone acetyltransferase opening chromatin

PER/CRY complex

blocks BMAL1/CLK via histone deacetylase

Clock‑controlled genes

contain E/E’ boxes; activated by BMAL1/CLK

SIRT1 activators

pharmacological modulators of circadian rhythms

Melatonin

hormone inducing sleep and synchronising clocks

Melatonin suppression

light suppresses melatonin

Melatonin use

treats sleep disorders; speeds jetlag recovery

Sildenafil effect

accelerates re‑entrainment after phase shift

Sildenafil mechanism

inhibits cGMP phosphodiesterase → increases cGMP in SCN

cGMP in SCN

modifies light‑induced phase shifts

Circadian timing consequences

metabolic coordination, seasonal timing, jetlag, chronotype, shift work