A GLOBAL GENETIC ANALYSIS OF NEMATODE SPLICED LEADER TRANS-SPLICING

Nematode worms are one of the most successful groups of animals in terms of absolute biomass and the occupation of a diverse range of habitats. The majority of nematodes are free-living, feeding on microorganisms, but a significant number are parasites of animals or plants. Nematode parasites of humans make a substantial contribution to the global burden of disease, with a handful of nematode species annually accounting for some 46 million disability adjusted life years (DALYs), and plant parasites are responsible for global crop losses estimated at $100 billion each year. Although there are some effective treatments for these parasites, increases in the number and distribution of strains that are resistant to these drugs mean that there is a need to develop new therapeutic treatments. Ideal targets for the development of new therapeutics would be molecules and processes that are found only in nematodes, but are absent from the animals and plants that they infect. Ideally the therapeutic target would be one that is found in all nematodes enabling the development of a drug active against a broad range of nematode infections. One such process is spliced leader trans-splicing, which is an essential part of the way that genes are expressed in nematodes. While we have a good understanding of the main events in this process there have been no systematic investigations into the molecules that are involved. We have identified a new experimental approach to investigate this process in the major experimental system used to study nematode biology, C. elegans. Using this system, we have shown for the first time that is possible to visualise, through changes in the expression of a fluorescent protein, alterations in spliced leader trans-splicing in living animals. We will use this breakthrough to better understand sliced leader trans-splicing, and thereby improve the knowledge upon which the development of new anthelmintic drugs depends.