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The Importance of Apoptosis: Insights from the Nobel Prize Winning Research

Apoptosis, or programmed cell death, is a crucial biological process for development and health. The 2002 Nobel Prize in Physiology or Medicine was awarded to Sydney Brenner, H. Robert Horvitz, and John Sulston for their groundbreaking work on the genetic regulation of organ development and apoptosis, utilizing the model organism Caenorhabditis elegans. This nematode, only 1mm long, offers insights into human health conditions, as many of its genes have human counterparts. Understanding apoptosis can help address diseases like cancer, ALS, and Alzheimer's by exploring gene activation and cellular programming.

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The Importance of Apoptosis: Insights from the Nobel Prize Winning Research

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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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