Each year up to one quarter of the world grain crop is lost during storage, a significant fraction of which is due to the insect attack reducing the grain quality and lowering the percentage of grains that germinate. The Australian grain industry is highly reliant on the fumigant phosphine for insect pest control with more than 80 per cent of the grain being treated with phosphine. The market demand for insect and chemical residue free grains has made phosphine an ideal fumigant for almost half a century. However, the high reliance on phosphine has resulted in selection of resistant insects of the major pest species. Additionally, very high-levels of resistance in some parts of the world poses a threat to the long-term use of phosphine due to increasing control failures. Since no equally effective alternative to phosphine exists, it is essential to understand the molecular basis of toxicity and resistance to design appropriate resistance management methods. The creation of phosphine-resistant mutants in the nematode Caenorhabditis elegans has allowed the use of this organism for exploration of the mechanisms of phosphine toxicity and resistance. Mutations causing phosphine resistance are located on genes which encode evolutionarily conserved mitochondrial enzymes: alh-6 encoding the delta-1-pyrroline-5-carboxylate dehydrogenase(P5CDH), an enzyme involved in catabolism of proline and dld-1 encoding dihydrolipoamide dehydrogenase (DLD), an enzyme that oxidizes dihydrolipoamide to lipoamide. Suppressing pest insect reproduction is a feasible management strategy to limit the proliferation and spread of insects carrying resistance alleles. We have addressed this by studying two situations that can be readily manipulated and that are commonly encountered by pests in grain stores, sublethal exposure to phosphine and mild thermal stress (elevated temperature). Interestingly we found sublethal exposure to phosphine caused a precipitous decline in fecundity in the wildtype and alh- 6(wr3) mutant strains, but caused a much weaker, dose dependent decrease in fecundity in the dld-1 phosphine resistant strain. This pronounced effect in alh-6(wr3) mutant strains may explain why the alh-6 mutation has not been identified in pest insects whereas the relative fitness of the dld-1 mutant in both high and low level phosphine exposure may favour rapid development of populations that carry this resistance factor. However, a mildly elevated temperature is sufficient to decrease the fecundity of the dld-1 mutant strongly and irreversibly in contrast to wildtype and the alh-6 mutant, which are only slightly affected. These results open the possibility that the resistant strains have certain vulnerabilities which could be exploited for better pest management practice such as through employing sublethal doses and elevated temperature or their combination to effectively suppress both resistant and susceptible phenotypes.This thesis focuses on the alh-6(wr3) mutant to explore the molecular basis of resistance through identifying potential candidate genes causing phosphine toxicity/resistance. This was achieved through gene expression profiling in either the absence or short-term presence of phosphine and the analysis indicates that the resistance in alh-6(wr3) is not induced by phosphine, but rather is due to strain difference. We have identified a set of genes associated with detoxification, metabolism, cellular signalling and behaviour/neural related differentially expressed between the strains. Most of the genes associated with cellular signalling and detoxification were strongly expressed in the mutant alh-6 whereas metabolism and behavioural/neural activity genes showed a reduced expression compared to the wildtype. The microarray analysis provides some insight into how the organism reacts to phosphine induced stress and has revealed possible candidate genes which can be used for further analysis. Surprisingly no genes associated with the alh-6(wr3) pathway were identified using gene expression analysis which motivated us to investigate the role of proline in phosphine resistance which forms the final part of this thesis. We found that although there is an increased level of proline in the mutant, genetic analysis does not support the interpretation that proline protects against phosphine-induced stress. The alh-6(wr3) mutant is also sensitive to various stresses that in other systems are ameliorated by proline. The mutant does, however have an increased lifespan compared to wildtype, which can be replicated by proline supplementation of the diet. Suppression of genes associated with the proline metabolic pathway suggests that the proline cycle may not be the major contributor to the resistance phenotype although the intermediate product P5C could be mediating the observed stress resistance. As a result of this work using the model organism C. elegans we have identified some of the practical strategies that may be useful for resistance management. Gene expression analysis has provided an insight into the resistance mechanism in the alh-6(wr3) mutant and has identified candidate genes for further analysis of the genetic pathways involved in phosphine resistance/toxicity.