Clockwork Genes: Discoveries in Biological Time

Lecture 3 – PERfect TIMing

by Michael Rosbash, PhD

  1.  1.  Start of Lecture 3
  2.  2.  Introduction by HHMI President Dr. Thomas Cech
  3.  3.  Introductory interview with Dr. Michael Rosbash
  4.  4.  Summary of the fruit fly's circadian clock
  5.  5.  Using attached-X-chromosome screening to find per gene
  6.  6.  Other approaches for finding new clock genes
  7.  7.  Drosophila DNA microarray used to assay RNA expression levels
  8.  8.  Currently known Drosophila clock genes
  9.  9.  Central pacemaker genes: clock and cycle
  10. 10.  Animation: Negative feedback by period protein (PER)
  11. 11.  timeless protein (TIM) and PER levels in a day
  12. 12.  TIM is degraded by light and stabilizes PER
  13. 13.  Animation: TIM causes PER feedback to be affected by daylight
  14. 14.  Q&A: Can you affect the master clock by affecting the clock in the liver?
  15. 15.  Q&A: How does light degrade the protein?
  16. 16.  Q&A: How many different RNAs do we know of?
  17. 17.  Q&A: Does light-related protein degradation happen in all cells?
  18. 18.  Q&A: Why is it necessary for two proteins to control the circadian rhythm?
  19. 19.  Q&A: Do any other external factors affect the system?
  20. 20.  The role of the kinase Doubletime (DBT)
  21. 21.  Cryptochromes: The light-sensitive protein as a candidate for circadian light sensor
  22. 22.  Are transgenic flies that have a double dose of the chryptochrome gene sensitive to light?
  23. 23.  cryptochrome mutant showing no circadian oscillations
  24. 24.  Constant light does not suppress the circadian rhythm of cryptochrome mutants
  25. 25.  Animation: DBT and cryptochrome protein's effects on circadian rhythms
  26. 26.  DBT mutant strain showing a long period
  27. 27.  Animation: DBT mutant kinase makes circadian period longer
  28. 28.  Description of some output genes, particularly pdf
  29. 29.  Experiment indicating the lateral neurons as the Drosophila pacemaker
  30. 30.  Summary of the Drosophila clock system
  31. 31.  Q&A: Have you substituted heat or other cues for light?
  32. 32.  Q&A: How does a circadian clock sustain the 24-hour cycle in the absence of light?
  33. 33.  Q&A: Do the pacemaker genes have a similar sequence to a mammalian gene?
  34. 34.  Closing remarks by HHMI President Dr. Thomas Cech

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