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

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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