Development of a novel platform for targeting animal parasites

Infections by intestinal parasites is a global problem that decreases animal health and food production. For example, in the UK, the cost of "wormer" or anthelminthic treatments and the loss of animal productivity for the sheep industry costs £84 million/year. In addition, resistance to most classes of anthelmintics is a growing problem. Therefore, sustainable control of these parasites would involve discovering new classes of anthelmintics. However, identification of drug targets and validation of these drug targets is difficult in parasites because they are difficult to culture due to their need for a host and their complex life cycles.
This project will develop an alternative worm model where we can identify novel classes of drug targets using a mix of data-mining and phenotypic screening of potential candidate proteins. The project will utilize two models: the simple nematode, Caenorhabditis elegans as a "stand-in" for parasitic worms to identify and "pre-screen" nuclear hormone receptor drug targets and a parasitic worm model to test these proteins in related cattle and sheep parasites for their ability to stop proliferation. We will attempt to validate a new class of putative drug candidates - namely the nuclear hormone receptors, which are a large class of proteins in C.elegans responsible for reproduction and metabolic regulation. In human, related nuclear hormone receptors are valuable drug targets for diseases such as cancer and metabolic disorders, suggesting that this conserved group of proteins may be good targets for modeling anti-proliferative drugs. Apart from validation of selected nuclear hormone receptors, this project will also give us insight into the functions of these proteins in the worm, where these are largely unknown.