Model Organisms in Drug Discovery

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Caenorhabditis elegans Functional
Genomics in Drug Discovery:
Expanding Paradigms
Titus Kaletta, Lynn Butler and Thierry Bogaert
In the past 10 years genomics has integrated rapidly into the process of drug
discovery. Consequently, a wealth of novel targets need to be validated and
screened to deliver more drugs in a shorter time. This asks for an animal
model that is complex enough to acknowledge the complexity of modern
medicine but also simple enough to be used in high-throughput applications.
Caenorhabditis elegans is the ideal model organism and was identified by
Sydney Brenner about 40 years ago. It is a spool-shaped worm ca. 1 mm long
with 959 cells that eats bacteria. It is genetically amenable and transparent, so
every cell division and differentiation could be followed directly under the
microscope. Brenner demonstrated in 1974 that mutations could be
introduced into many genes and visualized as distinct changes in organ
formation. Through his visionary work Brenner created an important research
tool: the nematode had made it into the inner circle of research and its utility
for biomedical research has just been awarded a Nobel prize. This chapter
describes C. elegans as a modern industrial tool for drug discovery. After an
introduction into the drug discovery process and into C. elegans, various
sections cover the design of C. elegans disease models, target identification
technologies and genome-wide target validation approaches. Subsequent
sections cover such topics as C. elegans compound assay design, C. elegans
high-throughput screening and C. elegans pharmacology. The reader will be
Model Organisms in Drug Discovery. Edited by Pamela M. Carroll and Kevin Fitzgerald
Copyright © 2003 John Wiley & Sons, Ltd. ISBN: 0-470-84893-6