Alistair Mathie

Biography

Alistair carried out his PhD research at the University of Leicester (1981-1984) supervised by Professor Asa Blakeley and Dr Stewart Petersen, and used intracellular electrophysiological recording techniques to study the electrical responses of sympathetically innervated smooth muscles, following neurotransmitter release at the neuroeffector junction. Following his PhD, he spent five years as a postdoctoral research associate in the laboratories of Professors David Colquhoun and Stuart Cull-Candy at University College London (UCL) studying the biophysical properties of ligand- and voltage-gated ion channels in single, isolated mammalian neurons using patch-clamp and whole-cell electrophysiological recording techniques. Then, from 1989-1991 he held a Fogarty International Research Fellowship at the University of Washington in Seattle, based in the laboratory of Professor Bertil Hille where the major focus of his research was to apply his experience in electrophysiology to study the intracellular mechanisms activated by neurotransmitters which couple to G-proteins and how these can regulate the activity of voltage-gated ion channels. In 1991, Alistair was appointed Lecturer in Pharmacology at the Royal Free Hospital School of Medicine then, following merger, a Senior Lecturer in Pharmacology at UCL. In 1999, he moved to Imperial College London where he took up a position there as Reader in Molecular Neuroscience. In 2007, he was appointed Professor of Pharmacology and Cell Biology, Head of Biological Sciences and Director of Research at the Medway School of Pharmacy.

Research Interest

The main research focus of Alistair’s laboratory is the study of mammalian cell excitability and how this is regulated. In particular, his major ongoing research theme is the determination of the roles of different ion channels in controlling the excitability and firing of mammalian cells, particularly neurons. Such ion channels are important in a variety of clinical conditions, such as epilepsy, stroke, neuropathic pain and depression and represent major potential therapeutic targets for future research. His laboratory uses a variety of state-of-the-art methodologies to study the properties of these ion channels, including whole-cell and single-channel patch clamp electrophysiology, two-electrode voltage clamp from oocytes, molecular biology (such as site-directed mutagenesis), fluorescent imaging of intracellular ions and fluorescently labelled proteins, tissue culture and computer modelling of ion channel structure and functional behaviour. Much of this work is done in collaboration with other laboratories and, currently, he has collaborative ventures with the pharmaceutical industry, academic laboratories elsewhere in the UK, and groups in Germany, USA and Australia. At present, we are studying the properties of potassium (K) channels in mammalian neurons and their modulation by various pharmacological agents, physiological mediators and neurotransmitter substances. We are also comparing the functional properties of certain native neuronal K channels with recombinant two pore domain K (K2P) channels such as TASK1, TASK3, TREK1, TRESK and THIK1. In a PNAS paper published in 2000, my laboratory identified a native leak K current in cerebellar granule neurons (which we named IKSO) which is critical in regulating the excitability of these neurons and correlated the properties of this current with those of the TASK family of K2P channels. Our work since then has contributed greatly to the detailed understanding of the properties and regulation of K2P channels in mammalian neurons, exemplified by our many publications over the last few years in high quality journals (see publication list for more details). As well as studying the structural, functional and expression properties of these K2P channels, we are investigating their role in a range of diverse physiological and pathophysiological conditions including depression, the detection and transmission of painful stimuli, programmed cell death and the development and maintenance of circadian rhythms. Our current work is supported by research grants from the BBSRC and the pharmaceutical industry.