Lecture 4: Chemical Genomics: New Tools for Medicine
by Stuart L. Schreiber, Ph.D.
Play Lecture Four in Full
Introduction by HHMI Grants Program Director Dr. Dennis Liu
Introductory interview with Dr. Stuart Schreiber
Chemical genetics used to explore many biological questions
Using genomics to investigate glucose sensing and type II diabetes
Concept of networks of proteins
Two networks are involved in the glucose-sensing system
Protein-to-protein interactions in the two networks
Network-to-network interactions at the node protein
Problems in the glucose-sensing system can cause Type II diabetes
Rapamycin can induce Type II diabetes
Finding new small-molecule probes with a small-molecule microarray
Animation: Small-molecule microarray
Limitations of the small-molecule microarray screening method
Overview of the cell-based screening method
Rapamycin-treated "diabetic" cells used to find probes that affect the network
Animation: Cell-based screening finds small-molecule inhibitor of rapamycin (SMIR)
Q&A: How do you know SMIR isn't directly affecting rapamycin?
Q&A: Does SMIR counteract the immunosuppressive effect of rapamycin?
Q&A: How can you find a common adhesive for all small molecules?
Q&A: Could you circumvent genetic defects by using small molecules?
Importance of information science and GenBank
Overview of the ChemBank project
How ChemBank works: Furrowstatin as an example
How ChemBank may help explain SMIR's action
Like genomics, Chembank shows the importance of global measurements
Concept of chemical space: Measuring small-molecule diversity
How diverse were the molecules synthesized by DOS in Lecture Two?
Computation could guide synthesis to evenly distribute molecules in chemical space
Could distinct regions of chemical space affect specific biological functions?
Possible example of Biology space: Blood-brain barrier
Animation: Future research may link between chemical space and biology space
Q&A: How long would it take to describe biology space?
Q&A: How are scientists sorting out different proteins?
Q&A: How widespread is ChemBank right now?
Q&A: Does rapamycin affect everyone's cells in the same manner?
Closing remarks by HHMI President Dr. Thomas Cech