Model organisms in genetics research: the nematode worm
Ben Stockton finds out how the nematode worm came to be a model organism
We have an extensive knowledge of a select group of animals, plants and microorganisms that are used in labs around the globe. The results of studies of these so-called ‘model organisms’ are used to help us understand biological phenomena in humans as well as animals.
At approximately 1 mm in length and transparent, the nematode worm known as Caenorhabditis elegans (C. elegans) might seem an unusual choice of animal to study in such detail. But this peculiar soil-dwelling roundworm has proved itself to be a vital research tool. In fact, it’s arguably the single most described animal in scientific literature.
Where did the nematode worm come from?
In the lab, the nematode worm lives on nutrient-enriched agar jelly in a Petri dish. But this clinical environment is worlds apart from its natural, and significantly more dirty, habitat. Although researchers had a wealth of knowledge about the genetics and physiology of the worm, its natural history has remained largely a mystery.
The wild-type (naturally occurring) strain of nematode worm that was used in the pioneering work of the mid-20th century was first located in British mushroom compost. These types of rotting environments are the Park Lane and Mayfair of the nematode Monopoly board, as they are rich in bacteria for the worms to feed on. By 1956, small-scale research on the nematode worm had begun in Berkeley, California.
Who were the pioneers in nematode worm genetics?
During the 1950s and early 1960s, researchers made a number of crucial discoveries in molecular biology. Suddenly the mysteries of biology seemed eminently solvable.
While working in Oxford, the South African researcher Sydney Brenner was one of the first people to see the structure of DNA, discovered by the Cambridge scientists Watson and Crick. Clearly impressed, Brenner soon moved to Cambridge and began working with Crick on bacterial genetics.
By early 1960, Brenner was looking for more complex biological problems, such as those in development and the nervous system. He wanted to apply the skills gained from studying bacterial genetics to multicellular life.
Drawing on the literature that had begun to emerge on the nematode worm, he concluded that it ticked all the boxes for his research (see below). This pivotal decision in 1963 has ultimately led to the research landscape we see today – within which the genome of the nematode has been completely sequenced and characterised.
Brenner remarked, after winning the 2002 Nobel Prize in Physiology or Medicine, that choosing the right organism became just as important as asking the right questions.
Why are nematode worms suited to genetics research?
The nematode worm offers simplicity to a researcher, as it has fewer than 1,000 body cells when fully grown. Despite lacking bones, a heart and a circulatory system, it has muscle, nerve and gut cells. It is also transparent, which means that its cellular activity can be easily observed.
The sheer scale of the work on nematode worms in the 1960s and 1970s (particularly that coming out of Cambridge) was one of the driving factors behind making the nematode worm a great model organism. The relationship between worm and scientist was relatively new, and this translated into a group of people excited about breaking new ground in the field of genetics.
Have nematode worms been used in any landmark studies?
Geneticists are working in a ‘post-genomic era’, in which the genome sequences of a significant number of organisms are known. The question now is: how can we find out what each of these genes does? As the first organism to have its whole genome sequenced, the nematode worm is the perfect candidate for research that tackles this question.
Two scientists, Craig Mello and Andrew Fire, developed a technique in nematode worms to help us better find out what specific genes are for. Using a technique called RNA interference, or RNAi, scientists can silence a specific gene, to give them an indication of what the function of that gene may be.
The beauty of the technique is that it’s relatively easy to do in nematode worms. By simply feeding the worms on bacteria containing a specific sequence of DNA, genes can be targeted for RNAi. This technique has revolutionised how we investigate the function of genes and ultimately can give an indication of which genes are affected by certain diseases. For this work, Mello and Fire shared the 2006 Nobel Prize in Physiology or Medicine.
What research in nematode worms is being done today and where is it going?
The nematode worm continues to be an important model organism. While it is especially challenging to unravel the mysteries of ageing in complex organisms such as humans, scientists are now looking at nematode worms in an attempt to understand, at a much more simple level, how living things age. Could this work eventually allow people to live to much older ages?
Dr David Becker/Wellcome Images
Questions for discussion
- The discovery of RNAi by Mello and Fire allows us to investigate genetic disease. Discuss how the ability to silence specific genes can allow us to investigate the causes of genetic diseases.
- Discuss what Brenner meant when he said that choosing the right organism can be just as important as asking the right questions in scientific research.
- Sydney Brenner on his life and pioneering research
- Animation on the process of RNAi
- Wellcome Trust film about the study of ageing in nematode worms
- Model organisms in genetics research: the mouse
- Model organisms in genetics research: the zebrafish
- Wave of blue fluorescence reveals pathway of death in worms