Many insect pests threaten crop production or are vectors of animal and human diseases and are therefore subjected to intensive insecticide treatments. This has resulted in the widespread evolution of resistance to these compounds, which curtails the use of particular chemicals and threatens the success of pest control programmes. Some of the most widespread and potent mechanisms of resistance result from modifications to the proteins targeted by different insecticide groups or by the detoxification of an insecticide before it reaches its target site. This project aims to elucidate these mechanisms at the biochemical and molecular level.

The target proteins studied include the voltage-gated sodium channel (the target of DDT and pyrethroids), acetylcholinesterase (the target of organophosphates and carbamates) and the nicotinic acetylcholine receptor (the target of neonicotinoids), all of which are important for functioning of the insect nervous system. The key objectives of this project are to characterise the insensitive proteins using a range of biochemical and molecular techniques and to clone the genes that encode the modified proteins and thereby identify the mutations responsible for resistance. We can confirm the functionality of these mutations by in vitro expression of the cloned genes, combined with site-directed mutagenesis, and thus identify the key regions/residues of the proteins that are involved in insecticide binding. A more detailed understanding of the key interactions between these insecticides and their target proteins can then be obtained using computer-based homology modelling.

For resistance by increased metabolism we are studying the enzymes responsible for this in a range of pest species. This involves biochemical characterisation of esterases and oxidases, including the effects of synergists which can block the detoxification enzymes and render 'resistant' insects sensitive to the insecticides.