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

A T

G C

C G

T A

A

G

C

T

T

C

G

A

T A

C G

G C

A T

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 Alcohol3. Pour alcohol (full bottle) into DNA4. Insert wooden end of toothpick into liquid5. Twirl stick You are spooling DNA!

You can repeat this experiment by takingthe DNA and placing it in water and a pinchof table salt. Let redissolve, add alcohol and repeat

Over 1000 organism’s genomes have been sequenced

599 viruses205 plasmids185 organelles3 eubacteria7 archae1 fungus (yeast)2 animals (worm and fly)1 plant (Arabadopsis)1 mammal (human)

Species Number of genesBacteria (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 Checkpointsand 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 chromosomesegregation

Distribution of Homologs

Prokaryotes only

Eukaryote and

prokaryote

No animal homology

Animals and other

eukaryotes

Vertebrate only

Vertebrates and other animals

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 dynamicsor 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 regimenIdentify 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-series0.75 µm apart

Compiled