Trends in Parasitology
ReviewCaenorhabditis elegans and the study of gene function in parasites
Section snippets
Parasite genome projects
Parasite genome projects are aimed at identifying key cellular functions that could lead to the identification of mechanisms of drug resistance, antigenic variation and genetic diversity, as well as the discovery of novel drug targets and antigens with diagnostic and/or vaccine potential. Large-scale sequencing of ESTs from different life cycle stages of Brugia malayi 5 and Onchocerca volvulus 6 are currently under way. In addition, EST surveys in Haemonchus contortus 7, Toxocara canis 8,
Functional genomics
The existence of a complete genome sequence of C. elegans and methods that support the rapid progress from a gene sequence to potential function have made it possible to assemble molecular outlines for many cellular and developmental processes. This has facilitated the study of the corresponding processes in parasitic nematodes, as exemplified by several studies on parasite cysteine and aspartyl proteases. Eukaryotic proteases of the cathepsin family have long been recognized for their role in
C. elegans as a heterologous transformation system
Caenorhabditis elegans has also been successfully used as a heterologous transformation system to study the function of parasitic nematode genes by investigating the expression of the parasite promoters in C. elegans (Table 1; Fig. 2). The activity of three different parasitic nematode gene promoters (pep-1, ac-2 and colost-1) have recently been examined in C. elegans using lacZ reporter constructs 36. All three promoters showed tissue-specific expression in the progeny of transgenic worms.
Chemotherapeutic targets
Caenorhabditis elegans has been widely used as a primary screen of compounds for toxicity in both human and veterinary medicine 3. Moreover, it provides a particularly convenient vehicle for investigating anthelmintic drug action and studying the mechanism of drug resistance. The benzimidazoles (BZ) are potent drugs for treating gut nematode infection of humans and domestic animals 41. They act by disrupting microtubule assembly through binding to the nucleotide-binding site of a specific
Vaccine targets
The most attractive targets for vaccine development in parasitic nematodes are the surface components and the excretory–secretory (ES) proteins, especially those that are expressed in a stage-specific manner 52. Although there is some variation in the morphology, there is a significant conservation in the biochemical and basic structural patterns between the surface components of C. elegans and parasitic nematodes, making C. elegans also a good model to study the composition and biosynthesis of
Conclusion and perspectives
The conservation of biological processes between C. elegans and parasitic nematodes extends the use of C. elegans as a molecular and genetic model for important veterinary and human parasites. The C. elegans genome sequence is a critical resource that parasitologists will continue to take advantage of to focus their research into areas in which the understanding of biological pathways and principles, including development and systemic processes, are more easily attained. We predict that
Acknowledgements
We acknowledge the financial support provided by the National Institute of Health (NIH) (research grant R21-AI48057) and thank Jing Liu and Yelena Oksov for their expert technical assistance.
Glossary
- Chemical mutagenesis
- Small, random alterations in the DNA sequence of an organism induced by chemicals such as ethylmethanesulfonate (EMS).
- Expressed sequence tags (ESTs)
- Short, single-pass DNA sequences obtained from either end of randomly selected cDNA clones.
- Rescue by complementation
- Introduction of a wild-type copy of a gene into its genetic mutant background and then using the rescue of the mutant phenotype as an assay for the function of the injected DNA.
- RNA interference (RNAi)
- Inhibition of
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