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DTSTART:20130331T030000
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DTSTAMP:20260504T160938Z
UID:500404509b8d0@ist.ac.at
DTSTART:20131014T163000
DTEND:20131014T173000
DESCRIPTION:Speaker: Barry G. Hall\nAbstract: Every year influenza vaccines
  are based on attempts to predict the short-term evolution of the influenz
 a\nvirus. Hospitals try to predict the evolution of antibiotic resistance 
 genes and to cycle the use of antibiotics\nin an effort to slow down the l
 ocal evolution of those genes. Those efforts are usually unsuccessful. To\
 nreliably predict the evolution of pathogens we must understand evolution 
 as a process\, understand the\nconstraints on that process\, and frame tha
 t understanding in a way that permits practical application of\nwhat we ha
 ve learned.\nI will discuss three experimental studies designed to inform 
 us about the evolution of new functions and to\nallow us to predict evolut
 ionary outcomes.\n(1) The EBG system followed the genetic\, biochemical an
 d molecular changes involved in the evolution of a\nnew lactose utilizatio
 n system in E. coli. A specific\, branching\, evolutionary pathway was dem
 onstrated\nthat led to a greatly expanded substrate range and a 20-fold in
 crease in lactase activity.\n(2) Point mutations that increase activity ar
 e one way that organisms can acquire new functions. The can\nalso evolve n
 ew functions by expressing normally silent operons that include several ge
 nes that are\nrequired for the new function. E. coli cannot utilize ?-gluc
 oside sugars\, but it possesses three separate\nsilent\, or cryptic operon
 s that when activated\, often by spontaneous insertion of mobile elements\
 , allow\nthe strain to grow on those sugars.\n(3) We developed an in vitro
  evolution system to predict the evolution of the TEM ?-lactamase antibiot
 ic\nresistance genes. After showing that our system faithfully mimicked na
 tural evolution\, we applied our\nsystem to predicting how TEM would evolv
 e to confer resistance to a new antibiotic\, cefepime. At that\ntime\, in 
 nature\, no TEM variant conferred clinical resistance to cefepime. We evol
 ved variants that\nconferred very high resistance\, and predicted the exac
 t pathway of amino acid substitutions needed to\nachieve the highest level
  of resistance. One of those substitutions was already present in a varian
 t that\nconferred sub-clinical resistance. Two years later the predicted s
 econd-step mutation was found in a new\nTEM variant that conferred clinica
 l resistance
LOCATION:Raiffeisen Lecture Hall\, Central Building\, ISTA
ORGANIZER:ihetzenauer@ist.ac.at
SUMMARY:Barry G. Hall: The Institute Colloquium: Predicting future evolutio
 n: experimental approaches\, pract
URL:https://talks-calendar.ista.ac.at/events/492
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