“It has not escaped our attention that the structure provides a mechanism for replication”

A T G C C G T A

AGCTAGCT TCGATCGA TA CG GC AT

Two breakthroughs Yellowstone DNA Sequencing

PCR Amplification of DNA

Spooling DNA 1.Open top of the bottle marked DNA. 2.Open top of the bottle marked Alcohol 3.Pour alcohol (full bottle) into DNA 4.Insert wooden end of toothpick into liquid 5.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 Number of genes Bacteria (E. coli) 4,000 Fungi (S. cerevisiae) 6,000 Worm (C. elegans) 20,000 Fly (Drosophila) 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

32% of human genes have homologues in fly, worm and yeast Of 1,308 protein families, only 94 are specific to vertebrates

We’re unique not because of the parts list, Rather how the parts are put together Only 5% of our genome codes for protein 50% of the genome is simple repeat sequence Our fossil record is exposed! 13 chromosomal rearrangements separate our chromosomes from the cat

Functional Assays Proteomics – Develop assays to study the function of 30,000 proteins Imaging Informatics – Protein location and dynamics or Where is everyone ? Bioinformatics – Mining the 3 billion bits of information in the genome

Jellyfish on the eastern shore

Genetic disease Map Clone gene Diagnostics Gene therapy Understand basic biologic defect Preventive medicine Pharmacogenomics Drug therapy Time

Paradigm Shifts in Biomedical Research Genetically based, individualized preventive medicine Shift from treating symptoms to genetic therapy 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

The Cell Cycle G1 DNA synthesis G2 Mitosis

Charles Darwin Gregor Mendel Barbara McClintock

Digital Imaging Microscopy Z-series 0.75 µm apart Compiled