Ginsenosides and P2X receptors: natural resources for microbial killing. Understanding their molecular basis using computational, biological and biophysical approaches (STOKES_U18DTP1)
- Research Area Bioscience for Health
- Partner The University of East Anglia (UEA)
Dr Leanne Stokes -
- Application Deadline 27/11/2017
Purinergic P2X receptors are ligand-gated ion channels involved in many physiological and pathophysiological processes. A number of selective pharmacological agents have been discovered and mapping drug binding sites is still in its infancy for this family of receptors. Ginsenosides are known to act as positive allosteric modulators at P2X7 receptors, making the receptor more sensitive to its ligand, ATP. The Stokes group is interested in studying the biological effects of ginsenoside modulation of P2X7 in immune cells and whether this action may underlie some of the reported immune boosting actions of ginsenosides in vivo. In collaboration with the Angulo group, this project will use a variety of 3D molecular modelling and molecular dynamics techniques to map out the molecular binding site for ginsenosides on P2X receptors. The binding site will be verified by biological experiments using a site-directed mutagenesis approach and novel biophysical approach using saturation transfer difference (STD) NMR spectroscopy. This project constitutes a unique opportunity for a student to be trained in a number of advanced biophysical, computational and biological techniques in two different laboratories within the School of Pharmacy at UEA gaining a unique and valuable skill set in natural product pharmacology and drug discovery.