Exploring Biodiversity: The Search for New Medicines

Lecture 4 – Eavesdropping on Tiny Conspiracies

by Bonnie L. Bassler, PhD

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  1.  1.  Start of Lecture 4
  2.  2.  Welcome by HHMI President Dr. Robert Tjian
  3.  3.  Profile of Dr. Bonnie Bassler
  4.  4.  Helpful and harmful bacteria use quorum sensing
  5.  5.  Notorious pathogenic bacteria
  6.  6.  Pathogenic strategies
  7.  7.  Pathogenic strategies under QS control
  8.  8.  Structures of QS signaling molecules
  9.  9.  Demonstration: Models of QS molecules
  10. 10.  Autoinducers allow for intra-species communication
  11. 11.  The Lux signaling cascade in low cell density
  12. 12.  Short RNA inhibits the cascade in low cell density
  13. 13.  Signaling cascade in high cell density
  14. 14.  Animation: The molecular cascade in bacterial quorum sensing
  15. 15.  Small RNAs also regulate genes in higher organisms
  16. 16.  Autoinducer 2 handles inter-species communication
  17. 17.  Two parallel QS circuits
  18. 18.  QS1 signals "self," QS2 senses "other"
  19. 19.  QS1 and QS2 differentially affect gene expression
  20. 20.  How antibiotics kill bacteria
  21. 21.  Can QS be used to treat bacterial infections?
  22. 22.  Q&A: Can pathogens sense when they are too virulent?
  23. 23.  Q&A: If you inhibit QS, would bacteria grow uncontrollably?
  24. 24.  Q&A: Would a QS-based treatment require a functioning immune system?
  25. 25.  Q&A: Do any diseases come from inter-species QS?
  26. 26.  Developing drugs for blocking either QS1 or QS2
  27. 27.  Two ways to generate candidate anti-QS drugs
  28. 28.  Rational design of anti-QS drug candidates
  29. 29.  Screening massive chemical libraries for drug candidates
  30. 30.  Video: Screening chemical libraries with robotics
  31. 31.  Bioluminescence as an assay for QS block
  32. 32.  Differentiating QS2 versus poison
  33. 33.  First screen finds potential QS2 blockers
  34. 34.  Second step screens out toxins
  35. 35.  Preclinical testing of new drug candidates
  36. 36.  Looking to nature for other ways to interfere with QS
  37. 37.  Multicellularity, bacteria, and human cells
  38. 38.  Inspired by nature and biodiversity
  39. 39.  Q&A: How do bacteria attack other species's QS molecules?
  40. 40.  Q&A: What are some of the side effects of antibiotics?
  41. 41.  Q&A: How many bacteria constitute a quorum?
  42. 42.  Q&A: Can we remove rather than block the QS signals?
  43. 43.  Closing remarks by HHMI President Dr. Robert Tjian


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