P01 - Analysis of ligand binding at human and insect nAChRs
nAChR-mediated effects, such as impairment of neuromuscular junctions and respiratory failure constitute a therapeutic gap in the treatment of organophosphate poisoning with nerve agents and pesticides.
Positive allosteric modulators (PAMs) that inhibit desensitization of human nAChR represent a promising therapeutic approach.
In addition, insect nAChRs constitute important targets for the development of safer and bee-friendly pesticides but their assemblies, structures and functions are currently little understood.
In the proposed project we will use a combination of electrophysiology, mutagenesis, and computer simulations to 1) develop models of insect nAChRs and 2) determine the binding sites and molecular mode of action of selected modulatory substances at human and insect nAChR subtypes and thus provide a basis for the development of improved pesticides and compounds for the treatment of organophosphate poisoning.