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SUMMARY:New Technologies in Bioseparations and Biosensing from Engineered 
 Multi-domain Self-modifying Proteins - David Wood – Dept of Chemical Eng
 ineering\, Princeton University
DTSTART:20070314T153000Z
DTEND:20070314T163000Z
UID:TALK6211@talks.cam.ac.uk
CONTACT:Vanessa Blake
DESCRIPTION:My laboratory applies protein engineering and genetics to the 
 development of new technologies in the areas of biosensing\, drug discover
 y\, bioseparations and bioprocessing.  By combining rational protein engin
 eering with a highly flexible and reversible genetic selection system\, we
  have been able to create unique and useful designer proteins based on nat
 urally occurring self-splicing proteins known as inteins.  In bioseparatio
 ns\, we have combined a previously developed pH-sensitive self-cleaving in
 tein with a variety of purification tags to produce simple and economical 
 methods for purifying recombinant proteins at a wide range of scales.  Our
  most recent work involves the development of self-aggregating\, self-clea
 ving protein purification tags\, which allow the efficient recovery and pu
 rification of native targets using simple mechanical means without the nee
 d for chromatography.  In biosensing\, we have developed an allosteric rep
 orter protein\, incorporating an intein\, that can be controlled by the ad
 dition of small molecule ligands.  We have used these to construct an E. c
 oli hormone biosensor that is able to detect hormone-like compounds in gro
 wth media.  Remarkably\, this simple bacterial sensor can differentiate ag
 onist from antagonist compounds and has been effective in detecting a wide
  variety of strong and weak estrogenic compounds.  These include a wide va
 riety of known drugs as well as estrogenic pollutants\, home products and 
 natural herbal remedies.  Indeed\, we were recently able to identify estro
 genic activity in two newly constructed compounds from an untested small l
 ibrary\, which have now been confirmed in human cell assays.  Applications
  of our designed protein are far-reaching\, and include drug discovery\, b
 iosensing\, targeted drug activation\, reversible knockouts for metabolic 
 research\, new genetic selection systems\, and advanced cellular control s
 trategies.
LOCATION:Lecture Theatre 1\, Department of Chemical Engineering
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