C.elegans, a small free-living soil nematode, serves as a good genetic model for many parasitic nematode species as it shows significant genetic similarity to these parasites. Parasitic nematodes cause considerable morbidity in humans and huge economic losses in both the livestock industry and the agriculture industry and anthelmintic resistance to existing drugs has been increasing. Therefore it has become absolutely necessary to find novel drug targets. One characteristic of a good drug target is specificity, a target that must be either absent in the host or have sufficiently different pharmacology.
noah-1 and
noah-2 encode nematode specific proteins that are predicted to be components of the cuticle. We have shown that RNA interference of either
noah-1 or
noah-2 results in defects in moulting, mobility, egg laying, pharyngeal pumping, development and feeding. Such adverse phenotypic effects when their expression is knocked down in C.elegans suggest that these genes are essential. Consequently, knowing their function can contribute to research into potential drug targets for the control of parasitic nematodes. In addition, the spatial expression pattern of
noah-2 suggests that this gene is exclusively expressed in the hypodermis and the cuticle. Moreover, it was found that the mRNA expression levels of
noah-1 and
noah-2 peak before each larval moult, but were down regulated between moulting events. The project currently focuses on three main objectives. The first objective is to further characterize the spatial expression pattern of
noah-2 in addition to
noah-1 using translational GFP reporter constructs. This will contribute to more detailed information about their cellular localization. The second objective is to characterize the temporal expression pattern of
noah-1 and
noah-2 using Real-Time PCR. This will quantify the amount of mRNA expressed at a particular time in development. And, the last objective is to determine the range of proteins that are able to interact with NOAH-1 and NOAH-2 using the yeast-two hybrid method. Once more information about the function of these genes and their protein products is obtained, it is possible that we may uncover pathways or potential protein interactions that NOAH-1 and NOAH-2 participate in. If these pathways are crucial for viability of the worms and are specific or selective in nature (e.g. enzymes), they may contribute to identifying new drug targets for parasitic nematodes.