The role of selected ligands in conformational changes and activity of G protein-coupled receptors (GPCRs).
|Title of the project||The role of selected ligands in conformational changes and activity of G protein-coupled receptors (GPCRs).|
|Primary and secondary scientific disciplines||biophysics, neurobiology|
|Description of the project|| Mosquitos are the primary vectors of diseases that affect roughly 700 million and kill a million people each year. Malaria remains a major killer of children under five years old, taking the life of a child every two minutes. Unfortunately, the most commonly used repellents (i.e. DEET) lose their activity as mosquitoes become resistant. Moreover, they are found to be neurotoxic for humans, especially for children. Therefore, there is a high need for a new generation of mosquito repellents.
G-protein coupled receptors (GPCRs) play a crucial role in signal transduction and are a target of 30-50% of all modern drugs. These receptors play a crucial role in the activity of both human and insect neuronal system. Recent studies indicate that one of repellents mode of action is the modulation of GPCRs but the precise mechanism remains obscure.
Using molecular dynamics and docking we investigate the conformational changes in GPCRs, in response to ligands binding. Knowing the molecular basis of these changes will facilitate finding compounds that would serve as selective malaria vectors repellents having no side effects in human.
Characteristics and the main objectives of the research project:
· Characterization of conformational changes in selected GPCRs in response to agonists and antagonists binding
· Preparation of the mosquito receptor model in the insect-like plasma membrane and comparison with the human model
· Electrophysiological study of the impact of the selected compounds on neuronal activity of Periplaneta Americana model organism
The project is conducted in cooperation with the University of Angers, France
Principal supervisor: Prof. dr hab. Wiesław Nowak