Using C. elegans to produce proteins from parasitic nematodes for research and therapeutic use

Aims

This project aims to replace the use of gerbils in the large scale manufacture of a nematode protein that has immunomodulatory properties and potential therapeutic applications.

Background

Parasitic filarial nematodes can be tolerated in human hosts for many years with little evidence of pathology. This appears to reflect a parasite-induced suppression of the host pro-inflammatory immune responses. In countries where parasitic infections are endemic, the incidence of allergic or autoimmune inflammatory diseases is relatively rare. One reason for this may be that parasitic nematodes have an important role in priming the host immune system and protecting from aggressive pro-inflammatory or aberrant inflammatory responses. The nematode glycoprotein ES-62 is thought to have a key role in this because of its immunomodulatory activities and its ability to interact directly with B lymphocytes, dendritic cells, macrophages and mast cells. In the mouse ES-62 is protective against collagen-induced arthritis, a model of rheumatoid arthritis.

ES-62 and other worm proteins are potential therapeutics for a range of diseases affecting the immune system. In the laboratory ES-62 can be obtained from Acanthocheilonema viteae, a parasitic nematode worm that grows in gerbils. Large numbers of gerbils (and mice) are euthanased to obtain the protein for research purposes. This project aims to investigate purifying ES-62 from the free-living nematode worm, Caenorhabditis elegans, as an alternative to using A. viteae grown in the gerbil. The ability to grow C. elegans in large volumes in the laboratory provides an opportunity for large scale production of ES-62 for therapeutic and commercial purposes that would require thousands of animals if rodents were used

Research details and methods

The research will investigate whether ES-62, with the appropriate post-translation modification and biological activity, can be produced and isolated from transgenic C. elegans. Activity will be tested by measuring inhibition of pro-inflammatory cytokine production in the human macrophage cell line, U937.