Transcript Paradigm Shifts in Biomedical Research

“It has not escaped our attention that the structure provides
a mechanism for replication”
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Two breakthroughs
DNA Sequencing
Yellowstone
PCR Amplification of DNA
Spooling DNA
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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