[
International C. elegans Meeting,
2001]
The technique of RNA interference (RNAi) has the potential to expedite the search for new drug targets in parasitic nematodes, and to assist in their validation. The sugar trehalose is claimed to have important functions in the physiology of nematodes whereas it is considered to be unimportant in mammals. In this study we are assessing trehalose metabolism in nematodes, using C. elegans as a model. We have shown that trehalose is synthesised by the nematode and is present at all life cycle stages; highest concentrations were observed in dauer larvae and eggs. The enzyme trehalase, which converts trehalose to glucose, is active at all stages of the life cycle; we have identified three biochemically distinct trehalase activities, each with different properties, in preparations from C. elegans . Four genes encode putative trehalases: F57B10.7, T05A12.2, W05E10.4 and F15A2.2. Using Northern analysis and RT-PCR we have shown that each of these genes is expressed at all life cycle stages. The synthesis of trehalose is catalysed by two enzymes, trehalose 6-phosphate synthase (TPS) and trehalose 6-phosphate phosphatase (TPP). Two genes putatively encoding TPS are present in C. elegans : ZK54.2 and F19H8.1. We have shown by RT-PCR analysis that both genes are expressed at all stages of the life cycle. The gene(s) putatively encoding TPP have not yet been identified. We are using RNAi to examine the effects of temporarily knocking down the expression of these genes, individually and in combination. This investigation has received financial assistance from the Australian Research Council and the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.