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Nobel prize 2017 (physiology or medicine) - Circadian rhythm

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Explanation of Nobel Prize in Physiology or Medicine 2017 Circadian Rhythm Explained
Topic: Discoveries of Molecular Mechanisms Controlling the Circadian Rhythm
Content: What is Circadian Rhythm?
Circadian Rhythm in Humans
Molecular Mechanism -Transcription-Translation Feedback Loop (TTFL)
Genes involved in Circadian Rhythm- PERIOD gene, TIM gene, CLK gene, CYCLE gene, CRY gene and DOUBLETIME protein

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Nobel prize 2017 (physiology or medicine) - Circadian rhythm

  1. 1. Discoveries of Molecular Mechanisms Controlling the Circadian Rhythm Nobel Prize in Physiology or Medicine 2017 www.biologyexams4u.com
  2. 2. Affiliation at the time of the award: University of Maine, Maine, ME, USA Affiliation at the time of the award: Brandeis University, Waltham, MA, USA, H H M I Affiliation at the time of the award: Rockefeller University, New York, USA Jeffrey C. Hall Michael Rosbash Michael W. Young Nobel Prize Winners 2017 Physiology or Medicine www.biologyexams4u.com
  3. 3. What is Circadian Rhythm? Mimosa plant leaves opens towards the sun during day time and close at dusk Experiment: Mimosa plant kept in constant darkness for several days to check the rhythm is due to sunlight and temperature Result: Mimosa plant kept in constant darkness for several days also showed the same daily rhythm suggesting the existence of a cell autonomous clock that can maintain the biological rhythm even under constant conditions. This is the Circadian rhythm www.biologyexams4u.com French astronomer Jean Jacques d’Ortous de Mairan( 1729)
  4. 4. Circadian Rhythm (Circa: around; dies: day in Latin) To adapt to such changes in light and temperature, organisms have evolved an internal biological clock that anticipates day/night cycles and helps them optimize their physiology and behavior. This internally generated daily rhythm is known as circadian rhythm www.biologyexams4u.com
  5. 5. Molecular Mechanism of Circadian Rhythm (Konopka and Benzer, 1971) showing change in the normal 24h cycle of pupal eclosion and locomotor activity Identified a common mutated gene in all three flies Period gene, the first gene identified dealing with circadian rhythm. This gene was later cloned and sequenced by Jeffrey Hall and Michael Rosbash,, and Michael Young PERIOD gene: the first gene identified Seymour Benzer www.biologyexams4u.com
  6. 6. Transcription-Translation Feedback Loop (TTFL) www.biologyexams4u.com Period (PER) gene, mRNA & protein: cycling of period mRNA and period protein PER protein shuttles btw nucleus and cytoplasm Accumulation of PER protein resulted in the reduction of period mRNA expression (negative autoregulatory feedback ) the peak of period mRNA levels occurred early in the night, several hours before the peak in PER protein abundance. TIM protein : coded by timeless gene can directly bind to PER protein. The interaction is critical for PER protein nuclear accumulation and repression of the period gene. Per gene Per mRNA Per protein Tim protein Nucleus Cytoplasm
  7. 7. Transcription-Translation Feedback Loop www.biologyexams4u.com How is Period and TIM gene activated? CLOCK (CLK) and CYCLE (CYC) protein interact with each other, and bind to specific elements in the period and timeless genes, thereby positively regulating their transcription. TIM and PER act as negative regulators of CLK activity, and by this, the circadian feedback loop is closed Per gene Per mRNA Per protein CLK: CLOCK CYC: CYCLE Nucleus Cytoplasm
  8. 8. Transcription-Translation Feedback Loop (TTFL) www.biologyexams4u.com How the transcription (Per mRNA) and translation (Per protein) synthesis is delayed? DOUBLETIME protein a kinase : coded by double time (DBT) gene that phosphorylates PER and increases its degradation light can activate the protein product of the cryptochrome cry gene (CRY) and promote its binding to TIM, leading to its degradation in the When morning arrives, TIM is degraded, leaving PER vulnerable to phosphorylation by DBT and subsequent degradation. Per gene Per mRNA Per protein Translational feedback Transcriptional feedback CLK: CLOCK CYC: CYCLE CRY: Cryptochrome Nucleus Cytoplasm
  9. 9. Importance of this Discovery
  10. 10. Please Don’t Forget to www.biologyexams4u.com Happy learning    Thank you so much for your support………

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