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

Lecture 4 – Chemical Genomics: New Tools for Medicine

by Stuart L. Schreiber, 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. Stuart Schreiber
  4.  4.  Chemical genetics used to explore many biological questions
  5.  5.  Using genomics to investigate glucose sensing and type II diabetes
  6.  6.  Concept of networks of proteins
  7.  7.  Two networks are involved in the glucose-sensing system
  8.  8.  Protein-to-protein interactions in the two networks
  9.  9.  Network-to-network interactions at the node protein
  10. 10.  Problems in the glucose-sending system can cause type II diabetes
  11. 11.  Rapamycin can induce type II diabetes
  12. 12.  Finding new small-molecule probes with a small-molecule microarray
  13. 13.  Animation: Small-molecule microarray
  14. 14.  Limitations of the small-molecule microarray
  15. 15.  Overview of the cell-based screening method
  16. 16.  Using rapamycin-treated "diabetic" cells to find new small-molecule probes
  17. 17.  Animation: Cell-based screening finds small-molecule inhibitor of rapamycin (SMIR)
  18. 18.  Q&A: How do you know SMIR isn't directly affecting rapamycin?
  19. 19.  Q&A: Does SMIR counteract the immunosuppressive effect of rapamycin?
  20. 20.  Q&A: How can you find a common adhesive for all small molecules?
  21. 21.  Q&A: Could you circumvent genetic defects by using small molecules?
  22. 22.  Importance of information science and GenBank
  23. 23.  Overview of the ChamBank project
  24. 24.  How ChemBank works: Furrowstatin as an example
  25. 25.  How ChemBank may help explain SMIR's action
  26. 26.  Like genomics, ChemBank shows the importance of global measurements
  27. 27.  Concept of chemical space: Measuring small-molecule diversity
  28. 28.  How diverse were the molecules synthesized by DOS in Lecture Two?
  29. 29.  Computation could guide synthesis to evenly distribute molecules in chemical space
  30. 30.  Could distinct regions of chemical space affect specific biological functions?
  31. 31.  Concept of biology space: The blood-brain barrier as an example
  32. 32.  Animation: Future research may link chemical space and biology space
  33. 33.  Q&A: How long would it take to describe biology space?
  34. 34.  Q&A: How are scientists sorting out different proteins?
  35. 35.  Q&A: How widespread is ChemBank right now?
  36. 36.  Q&A: Does rapamycin affect everyone's cells in the same manner?
  37. 37.  Closing remarks by HHMI President Dr. Thomas Cech


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