Processes at biological membranes are fundamental to biological systems, but are challenging to study at the structural level. We are studying two biological membrane systems. The first involves mechanistic studies of a human heart potassium membrane channel protein (HERG) using molecular modelling to assess the structural basis of drug-induced pathologies that result from interactions with HERG. These studies are done in collaboration with experimental electrophysiology analysis of HERG in Professor Hancox’s lab in Physiology in Bristol. A second project involves the development and mechanistic characterization of antimicrobial peptides that kill target bacteria by perturbing the cellular membrane. We use biophysical and microbiological methods to determine how natural and designed peptides form pores in target cell membranes.
Webpage: http://www.bristol.ac.uk/biochemistry/research/cd.html
References:
El Harchi A, Zhang YH, Hussein LK, Dempsey CE, Hancox, JC (2012) Molecular determinants of hERG potassium channel inhibition by disopyramide. J. Mol. Cell. Cardiol. 52, 185 – 195.
Zhang YH, Colenso CK, Sessions RB, Dempsey CE, Hancox JC (2011) The hERG K+ channel S4 domain L532P mutation: Characterization at 37°C. BBA Biomembranes.1808, 2477 - 2487.
Hawrani A, Howe RA, Walsh TR, Dempsey CE (2008) Origin of low mammalian cell toxicity in a class of highly active antimicrobial amphipathic helical peptides. J. Biol. Chem. 283, 18636-18645