Friday, June 18, 2010

Robert "Bob" Austin, Princeton, "Junior Mints"

Junior Mints: references a Seinfeld episode where Jerry and Kramer are watching a surgery, and Kramer flips a Junior Mint into the open wound...

Elephant in the room: evolution of a cancer to become resistant to therapy.

Statement: Evolution here is not random (!?).

Bacterial experiment to probe for accelerated and directed evolution of drug resistance: The Death Galaxy
  • attempt to realize the fitness landscape dynamics in a dD ecologywith a large range of stress gradients
  • Goal: evolve resistance to CIPRO (in bacteria)
    • CIPRO binds to a gyrase
    • bacteria evolves different forms of gyrases, and eventually one is resistant to CIPRO
  • Creating a stress gradient across a population on a 1-inch slide
    • Food on one side, cipro and food on other (10 ug/ml CIPRO -- high dosage)
  • Resistance to 10ug/ml CIPRO in 20 hours!
    • Resistant bacteria spread very quickly
    • Bacterial morphology different in different parts of gradient
Point:  by the time you've detected the cancer/infection, it's already spread throughout the organism...

Further research:
  1. vary initial population
  2. sequence!
  3. model dynamics as function of antibiotic stress
Questions from audience:
  • What happens when you change the topology/connectivity of the gradient?
  • Are the dynamics universal?  Do the results here apply broadly?
  • Do the resistant-allowing mutations already exist in the bacteria, or do they happen during the course of the experiment?

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