Nicotinic acetylcholine receptors nicotinic receptor molecular chaperones and mechanisms of insecticide action

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The focus of this research proposal is an important class of neurotransmitter receptor, the nicotinic acetylcholine receptors (nAChRs), which are target sites for two major classes of insecticide (neonicotinoids and spinosad). As with almost all classes of insecticides, major problems of resistance have now developed in insect field populations. A particular emphasis of this research proposal is to elucidate the mechanism of action of spinosad and to explore mechanisms of resistance to this insecticide. In parallel, studies will be undertaken to investigate the role of proteins involved in generating functional nAChRs. A goal of this second aspect of the proposed research project is to facilitate research aimed at elucidating the pharmacological diversity of insect nAChRs. Insect nAChRs are closely related to nAChRs expressed in the nervous system of vertebrates. Such receptors in humans have been implicated in disorders such as Alzheimer's disease and schizophrenia. Indeed, some of the research proposed in this application will focus on mammalian nAChRs and it is expected that the research findings may, in the longer term, have relevance to research aimed at discovery of drugs targeting human nAChRs.