Lecture 8 Introduction to Model Organisms

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22 Apr 2012
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Lecture 8 PHC320 Introduction to Model Organisms
Model organisms
1. Novel therapeutic Targets
2. Target Validation
Chemical biology/chemical genetics/chemical probes
Inhibit gene function (proteins) with small molecule
Try to understand gene function via genetic knockdown
Chemical genetics: genetics + small molecule to understand drug MOA
Genetics, Chemical probes: Study gene function
Use genetics to make mutations to uncover phenotype that helps understand gene
function.
Academic perspective in drug discovery objectives
1. Identify new chemical probes for biological investigation
2. Publish findings
3. Make proves publicly available
4. Result independent validation of chemical probe by independent labs
5. Results Learn new biology
6. Results generate pharma interest in novel target
Modern drug discovery has declined
1. Identify drugs against targets in vitro does not equate in vivo
2. Need novel therapeutic targets. Target/Drug space is biased. Lack of new targets
explored. Pharma focus on same genome.
3. Not enough understanding of cell biology
Yeast genetics
Facile genetics
Grows fast, cheap
Simplest eukaryote, most well-characterized
Approximately 45% human homology
Complete collection of gene knockouts
Chemogenetics
YKO collection
1. HIP
Drug target identification
Heterozygous strains deleted for essential genes
2. HOP (homozygous profiling)
Genes that buffer drug target pathway
Homozygous strains deleted for nonessential genes
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