Scanning Life's Matrix: Genes, Proteins, and Small Molecules

Lecture 2 – Probing Genes and Genomes

by Stuart L. Schreiber, PhD

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  1.  1.  Start of Lecture 2
  2.  2.  Introduction by HHMI President Dr. Thomas Cech
  3.  3.  Introductory interview with Dr. Stuart Schreiber
  4.  4.  If you want to understand life's processes, perturb them
  5.  5.  Proteins serve as the key mechanical components of life's processes
  6.  6.  Perturbing life's processes: The genetic approach
  7.  7.  Perturbing life's processes: The chemical genetic approach
  8.  8.  What are small molecules?
  9.  9.  Demonstration: Use of molecular models in chemistry
  10. 10.  Animation: How does a small molecule modulate a protein?
  11. 11.  Animation: How does a small molecule activate a protein?
  12. 12.  Video: Using small molecules to study the cleavage furrow of cell division
  13. 13.  Video: Furrowstatin can freeze the dynamic process of cell division
  14. 14.  Video: Furrowstatin perturbation is reversible
  15. 15.  Animation: Furrowstatin works by binding to nonmuscle myosin II
  16. 16.  Using the arrested furrow to study cell division
  17. 17.  Chemical genetics lets us study dynamic processes
  18. 18.  Q&A: Does furrowstatin inhibit furrow formation or furrow function?
  19. 19.  Q&A: Are small molecules useful for treating disease?
  20. 20.  Q&A: How do you figure out which small molecule to use?
  21. 21.  Q&A: Can you define again what small molecules are?
  22. 22.  Where do these small molecules come from?
  23. 23.  Rapamycin, a small molecule from nature
  24. 24.  Small molecules from laboratory synthesis
  25. 25.  Target-oriented synthesis and its limitations
  26. 26.  Introduction to diversity-oriented synthesis (DOS)
  27. 27.  DOS process 1: Split to many tubes and attach to plastic beads
  28. 28.  DOS process 2: Perform first reaction and split again
  29. 29.  DOS process 3: Perform second reaction and further reactions
  30. 30.  Animation: DOS matrix
  31. 31.  Recent advances allow one person to make 88,400 new compounds
  32. 32.  How do we discover which small molecules are useful?
  33. 33.  Animation: Screening small molecules with a protein
  34. 34.  Two screening methods for identifying small-molecule function
  35. 35.  Q&A: Do you accidentally make unexpected molecules?
  36. 36.  Q&A: Wouldn't sorting through molecules of DOS take a long time?
  37. 37.  Q&A: Where did you get the idea to use chemistry in biology?
  38. 38.  Q&A: Wouldn't rapamycin's immunosuppression cause other diseases?
  39. 39.  Q&A: Could more than one small molecule interact with the protein of interest?
  40. 40.  Closing remarks by HHMI Vice President Dr. Thomas Cech


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