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A Medical Universe in a Worm - AHFMR Magazine Winter 2000


Drs. Main and McGhee


A tiny worm, visible only with a microscope and consisting of slightly fewer than 1000 cells, yeilds powerful clues that help scientists unravel the mysteries of human biology. The worm, known as C. elegans, lives for only a few weeks. Its natural habitat is soil where it eats bacteria and produces about 300 offspring before it dies.

The short lifespan and simple, transparent structure of C. elegans make it a useful model in the science. Every cell division, from fertilized egg to adult worm, can be observed during the four days from egg to adulthood. C. elegans has many of the features of higher organisms

  • digestive tract (gut),
  • reproductive organs,
  • nervous systems,
  • muscles
Molecular biologists use it to pinpoint genes and proteins that may be similar to those found in human development. They have the advantage of knowing the lineage of each of C. elegans' 959 cells, thanks to pioneering work done two decades ago by Dr. John Sulston, head of the Sanger Centre in Cambridge, England. Dr. Sulston also led the effort to successfully decode the DNA (genetic material) of the worm's entire genome, completed December,1998.

Heritage researcher Dr. Jim McGhee has studied C. elegans, focusing on the similarities of gut development in the tiny worm and in higher organisms. Even by worm standards, the C. elegans gut is very simple. At the eight-cell stage of development, about one hour after fertilization, one of the eight cells will go on to become the entire gut.

"We identified several genes that are turned on only in the gut, and then studied what regulated those genes. We've identified what we think is a major regulatory gene in the gut. Without it, the worms are dead," says Dr. McGhee. "Now we are trying to find out what other genes are involved."

His colleague, Heritage researcher Dr. Paul Mains, also works with C. elegans to study embryo development, with a specific focus on the interactions of genes that make events happen at the appropriate times. Cell division, for example, takes two main forms. One is meiosis, the division of sex cells making egg and sperm. After the egg and sperm join at fertilization, another type of cell division-mitosis-begins, which results in all the other cells of an organism. Dr. Mains studies the signals that turn meiosis on and off and then turn mitosis on with the proper sequence and timing.

"When meiosis goes awry in humans," says Dr. Mains, "the egg ends up with too many or too few chromosomes. The mildest manifestation, an extra copy of one of the smallest chromosomes, results in Down Syndrome."

By manipulating the genetics of C. elegans, Dr. Mains can observe what the outcome will be. For example, at one point in embryogenesis, the ball of cells that is the embryonic worm must squeeze out into a tube shape. He has found that this process involves contractions similar to those which occur in the smooth muscles lining the gut, arteries, and veins in mammals. Smooth-muscle contraction is also linked to blood pressure control in mammals. When Dr. Mains isolated genetic mutations that were defective in the elongation process in the worm, he found biochemistry similar to that involved in mammalian blood pressure control. One of the worm genes Dr. Mains studies has been identified in mammals and has a direct role to play in lowering blood pressure.

Although C. elegans' 19,000 genes have been identified, sorting out how they work and interact with each other is a new level of complexity. The basic research conducted by Dr. McGhee and Dr. Mains could potentially yield new information about many human health conditions.

Dr. Jim McGhee and Dr. Paul Mains are Heritage Scientists with the University of Calgary's Department of Biochemistry and Molecular Biology. Both receive support from the Medical Research Council of Canada.

Worm Maestro

Heritage researcher Dr. Paul Mains recalls that as he finished his first post-doctoral fellowship, he attended an international meeting of "worm" scientists. "I remember sitting in on the meeting and thinking what a real community it was. Everyone knew each other and shared information before it was published." He credits the ground-breaking research conducted by Dr. Sydney Brenner in the 1960s on C. elegans as setting the collegial atmosphere for worm researchers everywhere. "Most people can trace their research career lineage back to Sydney Brenner, and so the field has been characterized by cooperation rather than competition."

Perhaps this spirit of co-operation comes not just from Dr. Brenner's formidable scientific ability but from his personality, a glimpse into which is provided by the entertaining columns he writes for the publication, Current Biology. To read his articles, you'll have to register with a password and ID at: www.biomednet.com and enter the search query "Sydney Brenner".


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