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Why is dying so important?
Rhonda Hummel
Nobel Prize for Physiology
or Medicine 2002
• Co-awarded on October 7, 2002
• For “genetic regulation of organ development and
programmed cell death”
• Sydney Brenner (English)
• H. Robert Horvitz (American)
• John Sulston (English)
Sydney Brenner H. Robert Horvitz John Sulston
Caenorhabditis elegans:
The Perfect Model
• A nematode approximately one mm long containing blood,
muscle, heart, nervous, as well as other tissues
• From fertilization to adult in three days
• Life span of two to three weeks
• Adult organism comprised of 959 cells
• During embryological development will form 1090 cells
• Approximately 40 percent of the worm’s genes are also
found in humans
• Responds to taste, smell, temperature, touch, and
possibly light
• So, where did the other 131 cells go?
The C. elegans Organism
The Fundamental
Genes Being Examined
• EGL-1…initiates apoptosis by inhibiting the normal restraining action of
CED-9 on CED-4
• CED-1…a cell surface phagocytic receptor that recognizes corpses
• CED-3…triggered by CED-4 resulting in highly destructive proteases
acting upon cell structure
• CED-4…acted upon by EGL-1; required in cell death
• CED-9… protects against cell death
So what’s the big deal with studying worms?
• EGL-1…has multiple mammalian killer gene counterparts
• CED-1…similar to human transmembrane protein SREC
• CED-3…human counterparts are called caspases which initiate
apoptosis; protein ICE
• CED-4…human counterpart called APAF1 which promotes caspase
activation
• CED-9…comparable to the human oncogene BCL-2 which blocks cell
suicide
How is this applied
to human conditions?
• Certain cancers…uncontrolled cell division versus
uncontrolled cell destruction
• ALS (Lou Gehrig’s disease)
• Myocardial infarction
• Cerebrovascular accident
• Alzheimer’s disease
• Embryological development
CED-4 translocates from mitochondria to nuclear
envelope during programmed cell death
All cells have been caused to initiate apoptosis. Red-CED-4 protein. Green-nuclear envelope
protein lamin. In normal embryos, CED-4 is located in the mitochondria.
Summary
• The 2002 Nobel Prize for Medicine or Physiology awarded for “genetic
regulation of organ development and programmed cell death”
• C. elegans used for its complexity but simplicity
• Specific gene activation contributes to the programming of cells to die
• This research can be applied to human gene control in development as
well as certain health conditions