Sydney Brenner pioneered the use of the Caenorhabditis elegans nematode worm as a model system primarily to understand the nervous system in the late 1960s. He chose C. elegans because of its many useful traits that include:
- a small size) ~1mm long)
- a 3 day life cycle
- simple anatomy) 959 cells)
- store by freezing
- easy transgenic manipulation
Sydney Brenner obviously made a wise choice with C. elegans. His seminal paper on ‘The Genetics of Caenorhabditis elegans’ was published in 1974 and is the foundation upon which most work on C. elegans is based. As of November of 2007, this paper has been cited in other papers 3631 times! For his work on the genetics of C. elegans and his contributions to our understanding of the genetic control of animal development, Sydney Brenner shared the Nobel Prize with Sir John Sulston and Robert Horvitz in 2002.
C. elegans would not be of such great interest if the simple animal did not have some biological relevance to higher organisms, including humans. Anatomically, it has many tissues and cell types that are similar to humans, including striated and non-striated muscles, 118 different neuronal classes (a total of 302 neurons), an epidermis (called a hypodermis in elegans), and a simple intestine for example. Genetically, the worm has much similarity with higher organisms, including homologs of most of the major signaling pathways (insulin, FGF, EGF, Wnt, Notch, TGF-beta etc) that control much of animal development. Approximately 32% of worm genes are thought to have a human ortholog, with the percentage of homologues being much higher. Biologically, there are many examples of similar regulatory mechanisms at work in analogous processes in worms and vertebrates, even though these two groups of animals are separated by roughly 500 million years of evolution!
single worm crawling (from Bob Goldstein's lab, UNC Chapel Hill)
Some examples of discoveries first made in C. elegans include:
- the discovery of microRNAs by Victor Ambros, Gary Ruvkun and colleages
- understanding the genetics of programmed cell death by Robert Horvitz and colleagues
- the discovery of RNA interference by Andrew Fire and Craig Mello (who one the Nobel Prize in 2006 for their discovery!)
- understanding the genetic control of ageing by Cynthia Kenyon and Gary Ruvkun
It is therefore always exciting when a new discovery is made with C. elegans, as it often foreshadows a better understanding of the biology of more complex animals.
C. elegans worms crawling around on lab Petri dish (from the Exploratorium: The museum of science, art and human perception at the Palace of Fine Arts, Sfan Francisco)