The present slides discusses about one of the exciting process in life- the biological rhythm. The 2017 Nobel Prize in physiology/medicine was shared by Michael Rosbach, Jeffrey C Hall and Michael W Young for their discovery of mechanisms controlling circadian rhythm. A humble attempt has been done by myself to explain the whole concept. Hope you enjoy and feel free to make clarifications.

1. Vinitha S Babu

2. How do organisms
maintain their sleep
pattern constantly?

3. How do
different
organisms
become active
at different
times of the 24
hour cycle?

4. Why do we
experience jet lag?

5.  Natural cycle of change in our
body’s chemicals or functions.
 Internal master “clock” that
coordinates the other clocks in
your body.
 Located in the brain, right above
the nerves where the eyes cross.
 It’s made up of thousands of
nerve cells that help sync your
body’s functions and activities.

6. Circadian rhythms: the 24-hour cycle that includes
physiological and behavioural rhythms like sleeping.
Diurnal rhythms: the circadian rhythm synced with day and
night.
Ultradian rhythms: biological rhythms with a shorter period
and higher frequency than circadian rhythms like alertness.
Infradian rhythms: biological rhythms that last more than 24
hours, such as a menstrual cycle.

7. A key feature of life on Earth is its capacity to
adapt to the environment.
Rotation of the Earth on its axis has lead to
profound changes in environmental light and
temperature , at any given location.
Hence, the need of an internal biological
clock.
This internally generated daily rhythm is known
as “circadian”, from the Latin words circa
meaning “around” and dies meaning “day”.

9. Ancient and conserved
throughout evolution.
Exists in life forms from
unicellular to all multicellular
organisms.
The building blocks
of a circadian
system consists of :
Oscillator
Zeitgebers
Output
mechanisms

10. Documented for a long
time.
Began with the
observation of leaf and
flower movements in
plants.
Leaves of mimosa plants
close at night and open
during the day.
Jean Jacques d’Ortous de
Mairan (1729) - suggested
an endogenous origin of
the daily rhythm.

11. Circadian Behaviour
Endogenous clock v/s reaction to external stimuli of a circadian nature
 Eventually, the existence of an endogenous circadian clock would
finally become well established.

12. Cell autonomous clock that can maintain the
biological rhythm under constant conditions.

14.  Experimented by:
 Seymour Benzer and his student Ronald
Konopka
 At the California Institute of Technology
 On studies to identify mutant fruit flies with
altered circadian phenotypes.
 Performed classical chemical based
mutagenesis.
 Isolated three different strains of mutant flies
showing alterations in the normal 24h cycle of
pupal eclosion and locomotor activity.

15. Arrhythmic Mutant
Days
No.
of
flies
per
hour

18.  Arrhythmic: Non sense mutation
 Shorter period of 19h: Missense mutation
 Longer period of 28h: Missense mutation
 Location: X chromosome
Complementation test three mutations @ same gene
 Finally, named the gene as period: the first clock gene.

19. PER
Pump
Gradient
Threshold
Dissipated
through
light
sensitive
channels

20. PER Proteoglycan
Facilitated formation
of inter-cellular
connections through
gap junctions

21. Period gene
mRNA showed circadian cycles of abundance which
occurred at night
PER Protein

23. Period mRNA Wild type PER protein
rescue cyclic mRNA expression
Nonsense mutation
Oscillating levels of period mRNA
accumulation of PER protein resulted in the
attenuation of period mRNA expression

24. Michael
Young
Timeless
TIM
protein
Circadian
rhythm

26. ????
Generate
24 hour
oscillation
Delay on
TTFL
Coupled
Transcripti
on
Translation

27. Involved regulated protein
phosphorylation
Degradation of TTFL components
Nuclear translocation
Other post-translational modifications

28. Michael Young
doubletime
DOUBLETIME (DBT)
PER PER
degradation
P

29. Light
CRY
Promote its binding to TIM
Proteasome
Degradation
Degradation
Low
PER

31. Drosophila-
PER & TIM
Arabidopsis-
PSEUDO‐RESPONSE
REGULATOR (PRR)-
MYB domain
transcription
factors
TTFL

32. Cyanobacteria:
sequential protein
phosphorylation
Eukaryotes:RBC
hyperoxidation of
peroxiredoxin
Transcription
independent
oscillation

33. Not one but many…Circadian system of an animal
resembles a clock shop
rather than a single clock

34. SCN: Suprachiasmatic
Nucleus

35.  Synchronized both by
SCN and
environmental cues.
 OB: olfactory bulb
 PVN:
paraventricular
nucleus
 PVT:
paraventricular
nuclei of the
thalamus
 MBH: mediobasal
hypothalamus
 Arc: arcuate
nucleus

39.  Sleep disorders
 Depression
 Bipolar disorder
 Cognitive function
 Memory formation
 Neurological diseases.
 Advanced or delayed sleep-wake
cycles (rare-due to mutations in
clock genes)
 Cancer
 Neurodegenerative diseases
 Metabolic disorders
 Inflammation

40.  The discovery of self-sustained transcription/ translation feedback
loops as the central component of the molecular mechanism by
which clock genes control circadian oscillations in cells and tissues
has led to a new paradigm in our understanding of how organisms
anticipate and adapt to the regular daily environmental cues such as
light.

41.  Physiological relevance of TTFL independent oscillation???
 Relation between central and peripheral clock and the multiple
ways by which local and external cues affect them???