As the use of C. elegans in science grew, a community formed among the worm’s researchers. The C. elegans community was quick to develop and share resources. The Worm Breeder’s Gazette is a semi-annual newsletter first published in 1975, which shares information of interest to the C. elegans community such as experimental techniques and new findings. The Caenorhabditis Genetics Center (CGC), founded in 1979, is a central repository from which researchers can order thousands of different strains of C. elegans for use in their own research.
From the early years, prominent researchers working with C. elegans believed strongly in sharing data both among researchers and with the public. This openness set the tone for the field of molecular biology more broadly; for example, open data sharing policies around the sequencing of the C. elegans genome encouraged the Human Genome Project to follow suit.
The worm community often had to build its own tools in order to share data on the scales its members desired. One big project was the creation of ACeDB (A C. elegans Database), a database management system capable of storing and displaying many different kinds of biological information about C. elegans, including its complete genome, in a user-friendly way. The current iteration of ACeDB, known as WormBase, contains the annotated genomes of C. elegans and related nematodes, information on every known C. elegans gene and its function, genetic maps, the C. elegans cell lineage and connectome, and much more. The ACeDB software was soon used to create similar databases for other model organisms. Such databases now exist for many different species, making detailed biological data widely available to everyone. These databases are also often used to share the latest research, maintain a consensus around scientific terminology and gene annotation, and provide educational resources on the model organism. Anyone looking for general information on C. elegans can also visit WormBook, an open access, online review of C. elegans biology.
With these resources and others, the C. elegans community fostered a culture of sharing and scientific openness that continues to this day.
A few of the many discoveries and further tool development
C. elegans research, with its wealth of experimental tools and methods, pre-existing data with which to build and test hypotheses, and a worldwide community happy to share resources, has been the source of many important discoveries over the years. Many of these discoveries have also added to researchers’ toolkits, providing new ways to experiment with C. elegans and other research specimens. A few of these myriad impactful discoveries are highlighted below.
Insights into development and programmed cell death
Brenner and two researchers whom he had mentored, John Sulston, then at the The Wellcome Trust Sanger Institute, and Robert Horvitz, then at the Massachusetts Institute of Technology (MIT), were awarded the first Nobel Prize for work done in C. elegans in 2002. When the researchers were creating the C. elegans cell lineage map, they saw that some cells created during development died off at particular moments, and that this programmed destruction of cells, called apoptosis, was an essential part of creating the adult body. They identified key genes that regulate apoptosis, and their work led to insights into the role of apoptosis in human development, as well as in health and disease. For example, cancer cells are able to avoid apoptosis, and many modern cancer therapies work by reenabling apoptosis of cancer cells.
Andrew Fire at the Stanford University School of Medicine and Craig Mello at the University of Massachusetts Medical School used C. elegans to discover RNA interference (RNAi), a process that cells use to stop genes from being expressed. RNAi became an important research tool after researchers figured out how to tailor RNAi to turn off genes that they are interested in studying in different cells and species. Researchers turn off a gene and see what changes, which helps them figure out the gene’s function. People have also found uses for RNAi in medicine and industry. RNAi is easy to use in C. elegans — researchers can apply it to worms by simply feeding them modified bacteria — so this tool made the worms an even better model for genetics research. Fire and Mellow earned a Nobel Prize for their discovery in 2006.
Introducing a new visual tag
C. elegans also contributed to the development of another popular and powerful research tool, green fluorescent protein (GFP). GFP is a protein first found in jellyfish. It glows green under certain light waves. Martin Chalfie at Columbia University showed in C. elegans that the genetic code for GFP could be added as a tag to genes of interest, and then the products of those genes would glow, providing researchers with a great visual marker of where and when the genes were expressed. Chalfie shared the 2008 Nobel Prize in Chemistry for this work, and researchers now frequently use GFP and similar molecules as visual markers in experiments across species and cell types.
A model for aging
In 1993, Cynthia Kenyon at the University of California, San Francisco and colleagues discovered that mutations to a single gene, daf-2, along with the normal activity of a second gene, daf-16, could more than double the lifespan of C. elegans. Kenyon and others intrigued by this discovery would go on to use C. elegans to ask questions about the molecular mechanisms governing aging. Researchers have also studied how equivalent genes affect aging in other animals, including humans.
A model for sex determination, reproduction, and development
C. elegans has been used to explore questions related to sex, reproduction, and development. Barbara Meyer, then at MIT, now at the University of California, Berkeley, discovered the mechanism of sex determination in the worm, and has uncovered mechanisms by which gene expression is regulated to compensate an animal having one or two X chromosomes. Other researchers have used C. elegans to make important discoveries about germ cells, the cells that give rise to eggs and sperm. Judith Kimble and John White, then at the MRC Laboratory of Molecular Biology, now at the University of Wisconsin–Madison discovered the first germline stem cell niche in C. elegans, which is the place where animals maintain a pool of stem cells with which to keep producing new germ cells over time. This finding had implications for fertility and regeneration research. Geraldine Seydoux at Johns Hopkins University has used C. elegans to investigate unique features of germ cells, as well as how sperm and egg interact and how the early embryo prepares to form a complex adult body.
Understanding sense of smell
Thanks in large part to C. elegans having such a well-mapped nervous system, the worm has been a common model for researchers studying how animals sense and respond to stimuli in their environments. Cori Bargmann, an alumna of Whitehead Institute, now at Rockefeller University, studies how C. elegans sense and process outside stimuli, how those stimuli can trigger changes in behavior, and how the brain can be rewired to modify behaviors over time. Bargmann’s research has particularly illuminated the worm’s sense of smell. She found the first evidence of a receptor for a specific smell, and her work more broadly shed light on how animals are able to recognize many different types of smells.
A rich history of discovery
This is just a small sampling of the important discoveries that have been made in C. elegans. WormBook has compiled a list of many such achievements, including the discovery of multiple key molecules and pathways present across animals.
Worms at Whitehead Institute
Michael uses C. elegans to study microRNAs.