Model Organisms in Drug Discovery

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124 DROSOPHILA – A MODEL SYSTEM Figure 5.2 Four types of genetic screens. (A) Classical screen for recessive mutations as performed by C. Nu¨sslein-Volhard and E. Wieschaus. (B) Screen for recessive mutations in tissue-specific mosaic animals. Homologous recombination at the FRT sites produces two types of cell clones: cells homozygous mutant for one chromosome arm and cells homozygous for a cell lethal (cl) that kills the twin clone. (C) Dominant suppressors (or enhancers) induced anywhere in the genome modify a sensitized genetic background, in this
EVOLUTIONARY CONSERVATION OF DISEASE-RELATED PATHWAYS 125 case the rough eye phenotype caused by ectopic activation of the Wnt pathway. (D) An EP overexpression screen. The EP element carries GAL4 binding sites (UAS sites) and a basal promoter that directs expression of any gene that happens to lie next to its insertion site. In combination with the tissue-specific expression of the GAL4 transcription factor that binds to the UAS element, the system is activated and allows the study of over- or misexpression phenotypes of tagged genes in the appropriate tissue. (See text for detail and references)
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Model Organisms in Drug Discovery M
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Copyright u 2003 John Wiley & Sons
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Contents List of contributors .....
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CONTENTS ix 7 Genetics and Genomics
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List of Contributors Hector Beltran
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LIST OF CONTRIBUTORS xiii Stefan Sc
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1 Introduction to Model Systems in
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Organism INTEGRATING MODEL ORGANISM
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INTEGRATING MODEL ORGANISM RESEARCH
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INTEGRATING MODEL ORGANISM RESEARCH
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10 GROWING YEAST FOR FUN AND PROFIT
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3 Caenorhabditis elegans Functional
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THE DRUG DISCOVERY PROCESS 43 thoug
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multivulva phenotype of Ras gain-of
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disease. These molecular targets ar
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FROM DISEASE TO TARGET 49 Figure 3.
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FROM DISEASE TO TARGET 51 Figure 3.
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signaling pathway. The third catego
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FROM DISEASE TO TARGET 55 resistant
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phenomenon was first observed in C.
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profiles. The C. elegans gene expre
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emerging technologies. Forward gene
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The compound library LEAD DISCOVERY
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LEAD DISCOVERY 65 previous section,
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LEAD DISCOVERY 67 Figure 3.5 Distri
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Compound learning set for assay val
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Page 85 and 86: REFERENCES 75 de Montigny, C., Blie
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Page 91 and 92: 82 DROSOPHILA AS A TOOL FOR DRUG DI
Page 109 and 110: 100 DROSOPHILA AS A TOOL FOR DRUG D
Page 127 and 128: 5 Drosophila - a Model System for T
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Page 151 and 152: CHEMICAL GENETICS 143 acid identity
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Page 155 and 156: about their function in a multicell
Page 157 and 158: REFERENCES 149 Han, Z. S., Enslen,
Page 159 and 160: REFERENCES 151 Rintelen, F., Stocke
Page 161 and 162: 6 Mechanism of Action in Model Orga
Page 163 and 164: INTRODUCTION TO COMPOUND DEVELOPMEN
Page 165 and 166: MODEL ORGANISMS ARRIVE ON THE SCENE
Page 167 and 168: ELUCIDATING THE MECHANISM OF COMPOU
Page 169 and 170: ELUCIDATING THE MECHANISM OF COMPOU
Page 171 and 172: A CASE STUDY FOR ALZHEIMER’S DISE
Page 179 and 180: NEW CHEMICAL GENETIC STRATEGIES 171
Page 181 and 182: A CASE STUDY FOR INNATE IMMUNITY 17
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GLOBAL GENE EXPRESSION STUDIES IN M
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As described above, the extensive i
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REFERENCES 179 Austin, J. and Kimbl
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REFERENCES 181 Hughes, T. R., Marto
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REFERENCES 183 Sin, N., Meng, L., W
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186 GENETICS AND GENOMICS IN THE ZE
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8 Lipid Metabolism and Signaling in
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FISH AS A MODEL ORGANISM 205 genes
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LIPID METABOLISM SCREEN 207 transpo
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LIPID METABOLISM SCREEN 209 Figure
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the embryo media containing radioac
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ZEBRAFISH AS A MODEL SYSTEM 213 Fig
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ZEBRAFISH AS A MODEL SYSTEM 215 Reg
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aspirin, which has potent inhibitor
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REFERENCES 219 Chau, I. and Cunning
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REFERENCES 221 Patrono, C., Patrign
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224 CHEMICAL MUTAGENESIS IN THE MOU
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252 SATURATION SCREENING OF DRUGGAB
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280 INDEX bupropion 92 busulfan 143
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282 INDEX Dscam 171 dual-energy X-r
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284 INDEX L-685,818 16 lead discove
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286 INDEX protein function 19-22 pr
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288 INDEX yeast (continued) functio
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