Rhonda Hummel Why is dying so important?

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