Better living through models

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Better living through models What our fellow
creatures can tell us about being human
Hilary Kemp Staff Scientist, Basic
Sciences Division, Fred Hutchinson Cancer
Research Center
Great moments in evolution
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What models can tell us about being human

• Development
• Disease
• Society
• Cancer

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What is a model?

• Biologically similar to humans
• Technical/ethical easier to study
• Lab animal -- for example

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Biology Supermodels
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The age-old chicken and egg question

• How do you get a chicken from an egg

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How do you make a baby?
?
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Running the numbers from 1 (egg) to how many?
school.discovery.com/clipart/clip/in-body-.html
cells in human body? a) thousands b)
millions c) billions (thousand
millions) d) trillions (million millions)
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Your body many cell types
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Human development
(Carnegie stages - postovulation/fertilization)
FETAL (WK 9-36) Organ systems continue to develop
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Modeling early development

• FISH HUMAN
• Water Air
• Fins Limbs
• Gills Lungs
• Scales Skin

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Possum pig deer cow dog bat rabbit
human
Pharyngula stage - when vertebrates are most
similar to one another Dev Biol 172 412 -
Haeckel reprint from 1891
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http//www.rochester.edu/College/BIO/labs/KaneLab/
theStuff/fishTL/index.html
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Zebrafish Human
1 day old 6 weeks 50 X longer!
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Sudden death in young athletes
Loyola Marymount University basketball star
Hank Gathers D. 1990 (23)
Celtics star Reggie Lewis D. 1993 (27)
Sergei Grinkov, 1988, 1994 Olympic figure skating
champion D. 1995 (28)
Greg Menton, U Massachusetts swimmer
water-polo player D. 1996 (20)
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HCM (familial hypertrophic cardiomyopathy)

• Inherited thickening of heart muscle
• Cause disorganized muscle cells
• Mutant heart muscle protein (troponin T)
• Hard to study rare (1500), variable, sudden

Normal heart HCM
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The mystery of Troponin T
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Fish as a heart model
Fish hearts beat at 1d not needed till day 5
Nature Genetics v31106 UCSD
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Genetic diseases caused by mutation
Change DNA Change protein radiation
levels chemicals
location metabolism
efficiency mistake destroy
Change DNA radiation
chemicals metabolism
mistake
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More than just deliciousWhats so special
about protein?What are proteins doing, really??
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Whats so special about protein?What are
proteins doing, really??
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Your body many cell types
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What makes them different?
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Why do we look different?Mutations in genes that
determine eye, hair, skin tone
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Why do we look different?Not all mutations are
bad
We are ALL mutants
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Human mutation studies are hard

• Some traits are complex (height, build)
• variation multigenic environment
• Generation time is SLOOOOOOOW
• maturity? gestation? progeny? lifespan?
• People are high maintenance lab animals
• deliberate exposure to mutagens frowned upon

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The grand-daddy of mutation models the fruit fly
Fast (10 days) Fertile (500/female) Easily
mutagenized X-rays chemicals Mutations in
single genes affect eye color body color wing
shape body bristles and many more
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AND the Nobel prize goes to

• Lee Hartwell (our fearless leader) for Yeast
  Mutants