The principal research interests of the Membrane Protein Group are in the pharmacology and characterisation of ion channels.
The cell membrane prevents molecules passing between the interior and exterior of the cell, except in a controlled way. Two types of structure allow molecules to pass, ion channels and transporters. Ion channels feature in a large number of diverse diseases (e.g. cystic fibrosis) as they work to control the excitability of a cell. By using techniques such as patch clamping of cells and planar bilayer analysis we can study the responses of whole cells and single channels to various drugs including newly synthesised designer chemicals.
Blood pressure and the Maxi K Channel
The Maxi K channel is a large calcium and voltage gated channel consisting of two different sub-units, α and b, these associate in cell membranes to control flow of potassium ions, which amongst other things, controls vascular tone (and blood pressure). Epidemiological evidence shows that women are less likely to suffer from high blood pressure than men and this has been attributed to the protective influence of oestrogens. We have been investigating the effects of oestrogen and membrane impermeant oestrogen derivatives on the Maxi K channel with the hope of developing a novel therapy for hypertension. This work is in collaboration with Dr Christy Hunter of the Chemical Biology research group and Dr H. de Wet, the Department of Physiology, University of Oxford.
A separate collaboration with Dr Peter Cragg has led to the development of artificial ion channels. It is hoped that these designer molecules will mimic the actions of naturally occurring membrane proteins. We use planar bilayer analysis to measure the electrochemical effects of inserting the artificial channel into a model cell membrane.
Drug resistance
In addition to ion channel work the group has been working with other classes of membrane proteins that are responsible for drug resistance in both cancer cells and the malarial parasite Plasmodium falciparum.
P-glycoprotein (P-gp) and pfCRT are responsible for resistance in cancer and malaria respectively. Whilst P-gp is a well known clinically relevant transporter of drugs, pfCRT is relatively poorly characterised to the point where it is not known if it is a transporter or a channel. Work on pfCRT has begun very recently and we aim to determine the identity of the protein and ultimately its mode of action in conferring chloroquine resistance to P. falciparum. Both of these projects are in collaboration with Dr Richard Callaghan of the Oxford Drug Resistance Group, University of Oxford.
Group members
Dr Marcus Allen, Senior Lecturer
Mrs Jacqueline Maher, PhD student (University of Brighton Studentship)
Mrs Khayzuran Iqbal, PhD student
Mr Mike Pettit Clinical Lecturer
Dr Adam Heikal Research Officer/Post Doctoral Research Assistant (previously a CASE award PhD student funded by EPSRC (with Sirius Analytical), currently funded by SEEDA PoC (South East of England Development Proof of Concept)
