1. ID- 4109 (Cognition) Term Presentation, Fall’13 Sandipan Dasgupta,10-MS-12 4 th Year UG, Department of Biological Sciences

2. Rhythms in Biology Chronobiology: 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

3. 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

4. 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

5. Period mutants in Drosophila Per L, Per S, Per O - 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

6. Transcriptional feedback model TimPer E Box Tim Per TimPer P dCYC dCLK Nucleus Cytoplasm DBT Degrade Image: Sandipan Dasgupta Cognition, Fall’13, IISER Kolkata P

7. 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

8. Transcriptional feedback model mCrymPer 1/2/3 E Box Cry Per CryPer P BMAL mCLK Nucleus Cytoplasm CK Degrade Very weakly Image: Sandipan Dasgupta Cognition, Fall’13, IISER Kolkata P

9. 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 Degrade Tim P CRY Image: Sandipan Dasgupta Cognition, Fall’13, IISER Kolkata

10. 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

11. Model for circadian activities Master oscillator Physiological changes (OUTPUT) Physiological changes (OUTPUT) Environmental stimuli (INPUT) Environmental stimuli (INPUT)

12. 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

13. 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

14. Thank you Cognition, Fall’13, IISER Kolkata