Drug Discovery and Genomics Globes药物基因组学金球奖.pptVIP

Drug Discovery and Genomics How the Sequencing of the Human Genome and Related Developments has Impacted Drug Discovery The Promise The Concern Bottom Line Topics What is Genomics ? What is the relationship between genes and disease? What are the steps in developing a drug? What impact has genomics had on the process of drug development? What is Genomics ? Study of information stored in the genome structural and functional information Structural genomics — the sequence Information is encoded linearly and digitally in four coding molecules-bases Three bases = codon = amino acid A number of codons strung together code for a gene which codes for a protein Functional genomics — what the genes do Structural Genomics: The Human Genome Three billion bases long (=800 Tanachim) Codes for 30,000 to 80,000 genes 23 chromosome pairs (24 in chimp) 97% of genome does not code for translatable protein products June 26, 2000: Clinton and Blair announce rough draft Functional Genomics Sequence/structural motifs in proteins ie functional class of protein Homology to model organisms/gene knockouts: worms, flies, mice, fish, etc. Antisense in cell culture Microarrays of gene expression Proteomics Pharmacogenomics Functional Genomics: Motifs Gene families Super families of related activities such as dehydrogenases, glucocorticoid receptor-like etc. Bioinformatic tools; data mining Functional Genomics: Microarrays of Gene Expression Functional Genomics: Model Organisms Functional Genomics: Proteomics Functional Genomics: Pharmacogenomics Relationship between Genes Disease Genes do not cause disease, defective genes cause disease One gene one enzyme (Beadle and Tatum 1940s) Mendelian inherited diseases Polygenic diseases Relationship between Genes Disease A gene is missing or defective Replace protein Replace activity Gene is overexpressed Develop inhibitors of synthesis or activity Poly-genic disease eg asthma where up to 15 genes may be involved Relationship betwee