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Rhonda Hummel

Apoptosis:. 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).

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Rhonda Hummel

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  1. Apoptosis: Why is dying so important? Rhonda Hummel

  2. Nobel Prize for Physiologyor 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)

  3. Sydney Brenner H. Robert Horvitz John Sulston

  4. 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

  5. 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?

  6. The C. elegans Organism

  7. 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

  8. 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

  9. How is this appliedto 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

  10. 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.

  11. 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

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