Model Organisms in Drug Discovery

146 DROSOPHILA – A MODEL SYSTEM
Figure 5.5 Effect of rapamycin and wortmannin on Drosophila development. Wild-type
Drosophila were grown in the presence of 50 mM rapamycin (Rapa) 300 mM wortmannin
(WM) or 5% DMSO as a control. Two days after eclosion, the weight of the flies was
measured
phenotype in conjunction with the available information of the MOA in
humans will provide information on which biological pathway is inhibited by
the drug. Testing different mutations in genes encoding pathway components
for resistance or hypersensitivity to the drug may further narrow down the
target or identify it directly. When the target cannot be identified through
existing mutations, mutations that render the flies resistant to the drug can be
selected. Some of these mutations will identify the gene target or a closely
associated protein. This approach has been used successfully for the
identification of insecticide targets such as Methoprene and Ivermectin
(Ashok et al., 1998; Kane et al., 2000).
5.4 Outlook
From all multicellular organisms, the unprecedented wealth of biological and
genetic information makes Drosophila a very promising tool for target and
lead discovery using classical and chemical genetics. The number of disease
models in Drosophila increases rapidly. These include models for a variety of
neurodegenerative diseases (Muqit and Feany, 2002), metabolic diseases such
as type 2 diabetes and various cancers. The availability of genetically
sensitized systems suitable for genetic and chemical screening offers a highly
synergistic approach to target and lead discovery. Over the past 20 years,
Drosophila research has revolutionized our understanding of developmental
biology like no other organism. We are convinced that the next 20 years will
see an equally strong impact of this small fly on pharmaceutical research. By
delivering in vivo validated targets and leads rich in biological information