My research project
Exploration of ion selectivity in the ENaC/DEG Family
Ion channels in living cells are examples of where quantum effects can play a role in biology. These proteins provide a selective conduction of ions across cellular membranes, which is crucial for cell survival. They are so important that they rank as the second most important target for the development of pharmaceutical drugs. However, the mechanisms behind their selectivity - e.g. how these proteins can perfectly discriminate between ions - is not entirely understood.
The aim of this exciting PhD is to investigate selectivity of sodium (Na+) within a specific channel family: the Epithelial Sodium Channel/Degenerin (ENaC/DEG) Family. Studies will be driven by two different but related approaches: simulation via computer modelling and experiments via electrophysiology. I will mainly be focused on the selectivity filter of the channels, which is generally the narrowest part of the pore and where the channel can discriminate different ions, even those of identical charge, allowing only the right one to pass through (in this case Na+). The motif in the ENaC/DEG Family is (G/S)XS, where X is a non-conserved residue within this ion channel family.
It has been stated that residues of the selectivity filter create an energy barrier that ions have to cross. The aim of my project is to simulate the ion flow through these energy barriers, whilst experimentally measuring electrophysiological currents. To investigate the mechanism, several parameters can be tested: different ions (Li+, K+, Ca2+), isotopes (6Li, 40K, 43Ca, 44Ca, heavy water), flow direction and phospholipid composition of the membrane.
Pharmacological characterization of CDX, a Candoxin-inspired antagonist of nicotinic acetylcholine receptors.
Supervisor: Prof. Kini R. Manjunatha