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ID- 4109 (Cognition) Term Presentation, Fall’13Sandipan Dasgupta,10-MS-124th Year UG, Department of Biological Sciences
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Rhythms in BiologyChronobiology:
Analysis of periodic changes in physiology, in response to external changes in the environment.
Circadian Rhythms:
Biological changes oscillating over a 24 hour time period.
Etymology: (Latin)
“Circa” : Around
“Dian” : Day
Image: MedIndia
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Why is Chronobiology important? Anticipate changes in the environment.
Attune its physiology and behaivor accordingly.
Survival advantage.
Prevalent across wide range of organisms.
Foraging
Sleep
Eclosion
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Drosophila – an ideal model to study circadian rhythms
• Circadian physiological activities.
• Can anticipate both daily cycles as well relative span of day and night.
• Internal “pacemaker”.
• Conserved clock to physiological output.
• Rapid generation of mutants.
• Multiple genetic tools.
• Homology with human genome.Image: SFARIGene
Fig: Drosophila melanogaster
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Period mutants in Drosophila• PerL, PerS, PerO - Mutations were mapped to single locus.• Pleiotropic effect: Eclosion, Locomotor activity, Feeding behaivor.• Seat of “Per” activity: A group of 20-30 lateral neurons in brain.• “Per” like proteins found in higher organisms.• Identification of other “rhythmic” genes , like “Timeless (Tim)”.
Fig: Actogram of WT and per mutant flies.
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Transcriptional feedback model
Tim PerE Box
Tim Per
Tim Per
Per P
dCYC dCLK
Nucleus
Cytoplasm
DBT
DBT
Degrade
Image: Sandipan Dasgupta
Cognition, Fall’13, IISER Kolkata
P
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Whereas in mammals….• First rhythm mutants – “Tau” mutants in hamster : Short rhythm.• Ablation of SCN: Arrthymicity in rodents.
SCN is the seat of rhythmicity in mammals ( rodents).
Short rhythms
WT SCN tau-/- SCN
Ablate Transplant
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Transcriptional feedback model
mCry mPer 1/2/3E Box
Cry Per
Cry Per
Per P
BMAL mCLK
Nucleus
Cytoplasm
CK
CK
Degrade
Very w
eaklyImage: Sandipan Dasgupta
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P
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Clock resetting• Phase advance and phase delay in response to unexpected
exposure to light.• Ignore lightning/moonlight (?) • Responsible for short-term adjustment in the physiology.• Acclimatization to new time zones.• In Drosophila, Tim – a light sensitive clock component.• However, light detecting component – Cry• Cry orthologue in mammals - ?
Tim DegradeTim
P
UCRY
Image: Sandipan Dasgupta
Cognition, Fall’13, IISER Kolkata
U U
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Global transcriptome analysis• Look for temporally varying transcripts and proteins.
• Identification of numerous genes like “Lark”, “Pdf”, “Takeout”.
• “Lark” and “Pdf” : Protein level changes, mRNA constantly produced (?).
• Organ specific rhytmns:
Molecular rhytms of various clock components not same in SCN and liver.
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Model for circadian activities
Master oscillator
Physiological changes
(OUTPUT)
Environmental stimuli
(INPUT)
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Clock controlled physiology• Circadian rhythms in adaptive evolution.
• Expression of nutrient channels (e.g Slowpoke)
• Expression of digestive enzymes (e.g Cholesterol synthesis )
• Activation of metabolites.
• Activation of pathways for excretion/degradation of endobiotics and xenobiotics.
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Prospects• Exhaustive identification of molecular mediators of biological
clock.
• Mapping clock compoments to the master oscillator.
• How clock signals to peripheral tissues?
• Neuroendocrine signaling?
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Thank you
Cognition, Fall’13, IISER Kolkata