9 (Cognition) Term Presentation, Fall’13 n Dasgupta,10-MS-12 UG, Department of Biological Sciences
Dec 24, 2015
ID- 4109 (Cognition) Term Presentation, Fall’13Sandipan Dasgupta,10-MS-124th Year UG, Department of Biological Sciences
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
Cognition, Fall’13, IISER Kolkata
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
Cognition, Fall’13, IISER Kolkata
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
Cognition, Fall’13, IISER Kolkata
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.
Cognition, Fall’13, IISER Kolkata
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
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
Cognition, Fall’13, IISER Kolkata
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
Cognition, Fall’13, IISER Kolkata
P
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
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.
Cognition, Fall’13, IISER Kolkata
Model for circadian activities
Master oscillator
Physiological changes
(OUTPUT)
Environmental stimuli
(INPUT)
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.
Cognition, Fall’13, IISER Kolkata
Prospects• Exhaustive identification of molecular mediators of biological
clock.
• Mapping clock compoments to the master oscillator.
• How clock signals to peripheral tissues?
• Neuroendocrine signaling?
Cognition, Fall’13, IISER Kolkata
Thank you
Cognition, Fall’13, IISER Kolkata