P01 - Generation of surrogate insect nAChR receptors for pesticide testing
Insect nicotinic acetylcholine receptors (nAChRs) are important targets for the development of safe and bee-friendly pesticides. However,their subunit assemblies, structures and functions are currently little understood because the expression of functional insect nAChRs in heterologous expression systems has been difficult.
In the proposed project we will use a combination of computer simulations, mutagenesis, biochemistry and electrophysiology to 1) generate chimeric and hybrid insect/human receptors with insect acetylcholine binding sites and 2) compare the molecular mode of action and potency of selected modulatory substances at these "surrogate"
insect and human nAChRs receptors. These studies should identify protein domains and mechmanisms that hamper insect receptor expression and provide a basis for the development of improved pesticides.