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Caenorhabditis elegans is a nematode worm, which is about a milimetre in length and free-living. (Unlike many other nematodes, C. elegans is not parasitic.) It has been used by the scientific community as a model organism since 1965. It fills this role well, as a result of the ease with which it can be bred and stored; its fast generation time; its simple, transparent body, which consists of about 1000 cells that do not change once the worm has matured; its basic neural and sensory system; and the fact that the vast majority of individuals are self-fertilizing hermaphrodites, which allows a genetically homogeneous population to be easily maintained.

The worm is also extremely simple to work with in the lab, as populations can be grown on agar plates or in liquid media, need only a lawn of E. coli for sustenance, and can even be stored for decades if frozen at –80°C or in liquid nitrogen. The full worm lifecycle, from spawning an F1 to spawning an F2, takes about a week, but worms are mature enough after 3 days for their expression patterns to be almost fully adult; thus the success or failure of transgenic constructs can be assessed at that time.

The transparent body of C. elegans allows fluorescent proteins to be used as markers that can easily be detected in any tissues, while keeping the worm completely intact. The worm’s simple nervous system allows it to react to basic inputs in an appropriate manner. For example, mechanoreceptor neurons allow the organism to realize when it bumps into something, and then to back up and turn. C. elegans is also capable of thermotaxis (towards a preferred temperature range), phototaxis (away from light), and chemotaxis (towards evidence of food, away from evidence of hazards, and towards its favourite pH). The organism's ability react to stimuli can be easily manipulated through the introduction of new elements into the sensory neurons (individual neurons can be selectively targeted using the appropriate promoter, as described in our article on the nervous system.) This represents a wealth of opportunities in synthetic biology, as what C. elegans perceives itself to be experiencing can be manipulated to achieve a desired behaviour. A genetically distinct hermaphrodite can be cultured in isolation to produce a genetically identical population that can be maintained with ease. This allows a line of transformed worms to be easily kept.

There are a number of further reasons as to why C. elegans is especially useful in the field of synthetic biology. It is relatively easy to transform (in addition to the week-long generation cycle, microinjecting the gonad with a plasmid is sufficient), has a fixed number of cells at maturity (959 somatic nuclei for the hermaphrodite and 1031 for the male), can have its genes selectively silenced through RNAi (which was discovered in C. elegans), and lives naturally in temperate soil (and so thrives at laboratory temperatures).

Developmental biologists have been attracted to C. elegans, in addition to all of the reasons above, because of a number of striking analogues that can be found between the nematode and other model organisms. Riddle et al. in 1.I of C. elegans II put it this way:

“Whether by chance or by design, basic biomedical research in the past 30 years has concentrated on a relatively small number of model systems (primarily prokaryotic cells, yeast, protozoans, C. elegans, Drosophila, Xenopus, Mus, primates, and mammalian cells in culture). Although these are quite different from each other, an astounding degree of connectivity between them has been revealed in the past decade. The emerging parallels between the development of the body plan in nematodes, flies, and mice (Ruvkun, this volume), and the fact that similar proteins are used for programmed cell death in both nematodes and humans (Hengartner, this volume), provide two examples.”

Most importantly, however, there is a high degree of portability of genes between different complex animals, including the worm. Transgenes containing G-protein coupled receptors from humans and mice have been introduced into C. elegans before, and remarkably these receptors were also able to interact with the native G-protein subunits and function in the intended fashion, despite hundreds of millions of years of divergent evolution. This suggests that much of the work we will do in this little nematode will still be relevant if and when synthetic biology as a whole shifts its focus to larger animals.

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