Caenorhabditis elegans is a species of nematode worm and is frequently chosen as a model organism to study human diseases.
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While not as sophisticated as a mammalian model, using C. elegans as a model organism has advantages including having all the physiological properties of an animal, the ability to replicate human diseases and a fast life cycle. C. elegans has been used as a model organism to study human diseases ranging from Parkinson’s disease to mitochondrial diseases, as well as studying the immune system.
What is C. elegans?
C. elegans is a species of nematode worm, and the adults are approximately 1mm in length with 959 somatic cells. Its transparent body consists of three layers; an epidermal layer, an intestinal layer, and a muscle layer.
Other systems such as the nervous system and reproductive systems are found between the three layers.
This means that there are physiological overlaps between humans and C. elegans, such as the digestive system, the nervous system, and the reproductive system. There have been observations that showed that C. elegans has the ability to recognize and react to things they do or do not like, indicative of a level of complex behavior.
The life cycle of C. elegans is around two to three weeks and starts with an egg leading to four larval stages before reaching maturity. C. elegans display two sexes; male or hermaphrodite. The hermaphrodites are able to self-fertilize and can give birth to hundreds of progeny.
This ability to self-fertilize is a useful tool for its use as a model organism, not only because these hermaphrodites can reproduce in high numbers quickly, but also because certain mutated strains of C. elegans may be paralyzed but do not need to find a mate to reproduce.
C. elegans can be grown in a petri-dish containing E. coli in the laboratory, as their natural diet is bacteria. Because of their small size, large numbers of C. elegans can be maintained in the laboratory without using a large number of resources.
It is also possible to maintain C. elegans in a “starved” state for months, or for longer storage it is possible to freeze C. elegans at -80°C.
The combination of these properties makes C. elegans a good candidate as a model organism to study human diseases.
C. elegans as a model for Parkinson’s disease
Parkinson’s disease is an age-related neurological disorder that affects movement. Its hallmarks are the formation of protein aggregates called “Lewy bodies” and the loss of dopaminergic neurons. There are genetic components to Parkinson’s disease as well, such as PARK1/α-synuclein.
Sequencing of C. elegans genome did not find orthologues for α-synuclein, therefore it is possible to use C. elegans as a model organism to study the effects of different α-synuclein variants by overexpressing these in the worms without having to consider the effects of background α-synuclein expression.
α-synuclein is an integral part of Lewy bodies, and mutations in the α-synuclein gene have been linked to Parkinson’s disease by promoting aggregation and dopaminergic neuron death. Using C. elegans as a model organism, various studies found that overexpressing wild-type and mutated α-synuclein in dopaminergic neurons resulted in dopaminergic neuron loss.
Initially, it was thought that the aggregation of α-synuclein and the formation of Lewy bodies changed the function of the neurons, eventually leading to neuron death. A study that used C. elegans as a model organism, however, showed that it was the soluble oligomers of α-synuclein which induced neurotoxicity rather than the insoluble aggregates.
C. elegans as a model for mitochondrial diseases
Mitochondria are responsible for providing the cell with energy by oxidative energy metabolism, in the form of ATP. There are diseases that can arise due to dysfunction of the mitochondria; these include deficiencies in oxidative phosphorylation, Leigh syndrome, metabolic disorders, and maple syrup urine disease.
Because of the function of mitochondria, cells and tissues which are affected tend to be those that rely on high rates of oxidative energy metabolism, such as muscles, kidneys, pancreatic β cells, and neurons.
Research using C. elegans has found that human genes responsible for a range of mitochondrial diseases have an orthologous gene in C. elegans, giving the possibility of using C. elegans as a model organism for studying mitochondrial diseases.
Studies have shown that when the expression of some of these genes were suppressed in C. elegans, it led to defects including not developing to sexual maturity and even death. Interestingly though, partially suppressing some of these selected genes actually increased the lifespan of C. elegans.
C. elegans as a model for immunology
The immune system is divided into innate and adaptive immunity, and in C. elegans only the innate immune response is seen; this includes antimicrobial molecules like lectins, lysozyme, and other antibacterial molecules. C. elegans can be used as a model organism to study the innate immune response to pathogens.
As C. elegans feeds on bacteria, it is easy to swap the standard E. coli used as feed for a pathogenic bacterium, such as Salmonella enterica. S. enterica has various serovars, and the response of C. elegans immunity to the Typhimurium serovar has been well studied.
This showed that p38 MAPK signaling cascade is a crucial component in the immune response against S. typhimurium, shown by the increased susceptibility of C. elegans with mutations in this cascade to S. typhimurium infection.
Conversely, C. elegans can also be used as a model organism to study how bacteria behave in a host during infection; for example, studies have shown that S. typhimurium virulence factors including PhoP/PhoQ and SPI-1 are expressed once S. Typhimurium colonizes C. elegans, and that these virulence factors are crucial for establishing an infection in C. elegans.
Sources
- Apfeld, J. and Alper, S. (2018) What Can We Learn About Human Disease from the Nematode C. elegans? Disease Gene Identification - Methods in Molecular Biology, vol 1706. Humana Press, New York, NY doi: 10.1007/978-1-4939-7471-9_4
- Harrington, A. J., et al. (2010) C. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease. Developmental Dynamics
- Maglioni, S. and Ventura, N. (2016) C. elegans as a model organism for human mitochondrial associated disorders. Mitochondrion https://doi.org/10.1016/j.mito.2016.02.003
- Marsh, E. K., and May, R. C. (2012) Caenorhabditis elegans, a Model Organism for Investigating Immunity. Applied and Environmental Microbiology DOI: 10.1128/AEM.07486-11
Further Reading