Clockwork Genes: Discoveries in Biological Time

Lecture 4 – The Mammalian Timekeeper

by Joseph S. Takahashi, PhD

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  1.  1.  Start of Lecture 4
  2.  2.  Introduction by Grants Program Director Dr. Dennis Liu
  3.  3.  Introductory interview with Dr. Joseph Takahashi
  4.  4.  Review: Animation of mammalian circadian neuroanatomy
  5.  5.  Genetic approaches in mice; the model mammalian system
  6.  6.  Mutagenesis in mice
  7.  7.  Genetic screens to isolate circadian clock mutants
  8.  8.  Genetic analysis of the circadian clock mutant
  9.  9.  Phenotype of an SCN neuron from a circadian clock mutant
  10. 10.  Impact of the Human Genome Project on clock research
  11. 11.  Positional-cloning analysis to map the Clock gene
  12. 12.  Using positional cloning and transgenic mice together
  13. 13.  Map of the Clock gene region
  14. 14.  Structure of the Clock protein (CLOCK)
  15. 15.  Q&A: What would you do after understanding the mechanism of the biological clock?
  16. 16.  Q&A: Can you phase-shift a mammal with blue light?
  17. 17.  Q&A: Have you done overexpression experiments with Clock?
  18. 18.  Q&A: What experiments do you use to see the difference between mutant and wild-type genes?
  19. 19.  Q&A: What other kinds of mutations are there in the Clock gene?
  20. 20.  Function of CLOCK
  21. 21.  Nine different proteins related to circadian clock genes
  22. 22.  Cryptochrome 1 and 2 genes
  23. 23.  Animation: Role of Period (Per) and Cryptochrome (Cry) genes
  24. 24.  tau mutant in the golden hamster
  25. 25.  Identifying the gene involved in the tau mutant
  26. 26.  Biochemical basis of tau mutation on Casein kinase 1, epsilon gene
  27. 27.  Animation: Role of Casein kinase gene
  28. 28.  The effect of tau mutation on the Period gene's expression level
  29. 29.  Animation: tau mutation causes early buildup of negative feedback proteins
  30. 30.  Summary and comparison of mammalian and fly clocks
  31. 31.  Video: Interview on how per and other genes relate to humans
  32. 32.  A human sleep disorder related to circadian clock
  33. 33.  Summary of the four lectures
  34. 34.  Q&A: How do Cryptochrome double mutants behave in light/dark cycles?
  35. 35.  Q&A: Does temperature affect the circadian rhythm in mammals?
  36. 36.  Closing remarks by HHMI President Dr. Thomas Cech


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