Rhonda Hummel

Why is dying so important?

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)

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 The C. elegansC. elegans Organism 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 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

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