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“It has not escaped our attention that the structure provides a mechanism for replication” A T G C C G T A A T A T G C G C C G C G T A T A Two breakthroughs DNA Sequencing Yellowstone PCR Amplification of DNA Spooling DNA 1. 2. 3. 4. 5. Open top of the bottle marked DNA. Open top of the bottle marked Alcohol Pour alcohol (full bottle) into DNA Insert wooden end of toothpick into liquid Twirl stick You are spooling DNA! You can repeat this experiment by taking the DNA and placing it in water and a pinch of table salt. Let redissolve, add alcohol and repeat Over 1000 organism’s genomes have been sequenced 599 viruses 205 plasmids 185 organelles 3 eubacteria 7 archae 1 fungus (yeast) 2 animals (worm and fly) 1 plant (Arabadopsis) 1 mammal (human) Species Bacteria (E. coli) Fungi (S. cerevisiae) Worm (C. elegans) Fly (Drosophila) Number of genes 4,000 6,000 20,000 12-14,000 Plant (Arabidopsis) 25,000 Mouse 30,000 Human 30,000 The Discovery of Cell Cycle Checkpoints Checkpoint mutants: Live Hard and Die Fast Cell Cycle Checkpoints and Cancer Checkpoints ensure that cells complete one event before proceeding to the next event Cancer is a disease of uncontrolled cell growth, sloppy DNA replication and errors in chromosome segregation Distribution of Homologs Vertebrates and other animals No animal homology Animals and other eukaryotes Vertebrate only Prokaryotes only Eukaryote and prokaryote 32% of human genes have homologues in fly, worm and yeast Of 1,308 protein families, only 94 are specific to vertebrates • Only 5% of our genome codes for protein • 13 chromosomal rearrangements separate our chromosomes from the cat • 50% of the genome is simple repeat sequence Our fossil record is exposed! We’re unique not because of the parts list, Rather how the parts are put together Functional Assays Bioinformatics – Mining the 3 billion bits of information in the genome Proteomics – Develop assays to study the function of 30,000 proteins Imaging Informatics – Protein location and dynamics or Where is everyone ? Jellyfish on the eastern shore Genetic disease Time Map Clone gene Understand basic biologic defect Diagnostics Preventive medicine Pharmacogenomics Gene therapy Drug therapy Paradigm Shifts in Biomedical Research Shift from treating symptoms to genetic therapy Genetically based, individualized preventive medicine Determine genetic profile for battery of diseases Pharmacogenomics- prophylactic drug regimen Identify disposition of offspring THANKS !!! Special thanks to John Anderson Purdue University Rachael Bloom Paradigm Shifts in Biomedical Research Structural genomics Functional genomic Genomics Proteomics Map-based gene discovery Sequence-based discovery Monogenic disorders Multifactorial disorders Specific DNA diagnosis Monitoring of susceptibility Analysis of one gene Analysis of multiple genes Gene action Gene regulation Specific mutations Mechanism One species Several species G1 DNA synthesis Mitosis G2 The Cell Cycle Gregor Mendel Charles Darwin Barbara McClintock Digital Imaging Microscopy Z-series 0.75 µm apart Compiled