Position Available - Wim Hol (1)

Heidi Singer hragland at u.washington.edu
Tue Jul 10 19:06:59 EST 2001


POSITION OPEN:  POSTDOCTORAL FELLOW - Crystallography of Cholera Toxin
Inhibition

JOB DESCRIPTION:  Applications are invited for a postdoctoral position
in Wim Hol's group on a project aiming at the structure-based design of
novel inhibitors of cholera toxin and its close relative heat-labile
enterotoxin.  These toxins are responsible for a large number of victims
among young children in developing countries as well as in natural
disaster areas.
     The toxins have a most unusual heterohexameric AB5 architecture, an
intriguing assembly mechanism, and a fascinating mode of action.  One of
the goals of our interdisciplinary project is to arrive at ultra-high
affinity receptor antagonists of the B-pentamer.  Another one is to
design inhibitors of the assembly mechanism.  Excellent expression and
purification protocols are already in place.  A team of groups including
chemists and molecular modelers is designing and synthesizing new series
of compounds whose precise mode of binding to the target toxin will be
studied by protein crystallographic techniques.
 The studies involved will include:
(i) protein crystallographic methods to unravel structures of
protein-ligand complexes, with some of the ligands being over 10 kDa.
(ii) molecular modeling methods to guide the design and synthesis of
improved ligands.
     Knowledge of protein crystallographic methods is essential and
experience in molecular modeling techniques would be very welcome!

INSTITUTION:   Department of Biochemistry & Howard Hughes Medical
Institute
                           Biomolecular Structure Center
                           School of Medicine
                           Box 357742
                           University of Washington
                           Seattle, WA, 98195  USA

SCIENTIFIC ENVIRONMENT: The research will take place within the
framework of the Biomolecular Structure Center of the University of
Washington. The Center brings together several groups involved in
Structural, Chemical and Computational Biology and is well equipped with
area detectors, calorimeters, fluorimeters, chromatography systems and
state of the art instruments for protein expression, purification and
crystallization. The School of Medicine of the University of Washington
provides an exceptionally rich scientific environment. In addition,
close interactions exist with the Department of Chemistry in relation to
several structure-guided drug design projects.

WHAT TO DO: Please send a full CV, list of publications, a brief
description of research interests and experience, plus a list of three
references by mail or email to Wim Hol.

PHONE:  206-685-7044
FAX:  206-685-7002
EMAIL:  hol at gouda.bmsc.washington.edu
WEBSITE:  http://www.bmsc.washington.edu/WimHol







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